|
1
|
Laganà A, Visalli G, Facciolà A, Saija C, Bertuccio MP, Baluce B, Celesti C, Iannazzo D, Di Pietro A. Sterile inflammation induced by respirable micro and nano polystyrene particles in the pathogenesis of pulmonary diseases. Toxicol Res (Camb) 2024; 13:tfae138. [PMID: 39233846 PMCID: PMC11368663 DOI: 10.1093/toxres/tfae138] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/07/2024] [Revised: 07/24/2024] [Accepted: 08/26/2024] [Indexed: 09/06/2024] Open
Abstract
Sterile inflammation is involved in the lung pathogenesis induced by respirable particles, including micro- and nanoplastics. Their increasing amounts in the ambient and in indoor air pose a risk to human health. In two human cell lines (A549 and THP-1) we assessed the proinflammatory behavior of polystyrene nanoplastics (nPS) and microplastics (mPS) (Ø 0.1 and 1 μm). Reproducing environmental aging, in addition to virgin, the cells were exposed to oxidized nPS/mPS. To study the response of the monocytes to the inflammatory signal transmitted by the A549 through the release of soluble factors (e.g. alarmins and cytokines), THP-1 cells were also exposed to the supernatants of previously nPS/mPS-treated A549. After dynamic-light-scattering (DLS) analysis and protein measurements for the assessment of protein corona in nPS/mPS, real-time PCR and enzyme-linked-immunosorbent (ELISA) assays were performed in exposed cells. The pro-inflammatory effects of v- and ox-nPS/mPS were attested by the imbalance of the Bax/Bcl-2 ratio in A549, which was able to trigger the inflammatory cascade, inhibiting the immunologically silent apoptosis. The involvement of NFkB was confirmed by the overexpression of p65 after exposure to ox-nPS and v- and ox-mPS. The fast and higher levels of IL-1β, only in THP-1 cells, underlined the NLPR3 inflammasome activation.
Collapse
Affiliation(s)
- Antonio Laganà
- Department of Biomedical and Dental Sciences and Morphofunctional Imaging, University of Messina, Via Consolare Valeria, 98125 Messina, Italy
- Istituto Clinico Polispecialistico C.O.T. Cure Ortopediche Traumatologiche s.p.a., Viale Italia, 98124 Messina, Italy
| | - Giuseppa Visalli
- Department of Biomedical and Dental Sciences and Morphofunctional Imaging, University of Messina, Via Consolare Valeria, 98125 Messina, Italy
| | - Alessio Facciolà
- Department of Biomedical and Dental Sciences and Morphofunctional Imaging, University of Messina, Via Consolare Valeria, 98125 Messina, Italy
| | - Caterina Saija
- Department of Biomedical and Dental Sciences and Morphofunctional Imaging, University of Messina, Via Consolare Valeria, 98125 Messina, Italy
| | - Maria Paola Bertuccio
- Department of Biomedical and Dental Sciences and Morphofunctional Imaging, University of Messina, Via Consolare Valeria, 98125 Messina, Italy
| | - Barbara Baluce
- Department of Transfusion Medicine and Hematology and Lombardy Regional Rare Blood Bank, IRCCS Ca’ Granda Ospedale Maggiore Policlinico, Via Francesco Sforza, 35, 20122 Milan, Italy
| | - Consuelo Celesti
- Department of Electronic Engineering, Industrial Chemistry and Engineering, University of Messina, Via Stagno d'Alcontres, 98125 Messina, Italy
| | - Daniela Iannazzo
- Department of Electronic Engineering, Industrial Chemistry and Engineering, University of Messina, Via Stagno d'Alcontres, 98125 Messina, Italy
| | - Angela Di Pietro
- Department of Biomedical and Dental Sciences and Morphofunctional Imaging, University of Messina, Via Consolare Valeria, 98125 Messina, Italy
| |
Collapse
|
|
2
|
Wan XX, Hu XM, Zhang Q, Xiong K. Pretreatment can alleviate programmed cell death in mesenchymal stem cells. World J Stem Cells 2024; 16:773-779. [PMID: 39219726 PMCID: PMC11362856 DOI: 10.4252/wjsc.v16.i8.773] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/13/2024] [Revised: 07/04/2024] [Accepted: 07/26/2024] [Indexed: 08/26/2024] Open
Abstract
In this editorial, we delved into the article titled "Cellular preconditioning and mesenchymal stem cell ferroptosis." This groundbreaking study underscores a pivotal discovery: Ferroptosis, a type of programmed cell death, drastically reduces the viability of donor mesenchymal stem cells (MSCs) after engraftment, thereby undermining the therapeutic value of cell-based therapies. Furthermore, the article proposes that by manipulating ferroptosis mechanisms through preconditioning, we can potentially enhance the survival rate and functionality of MSCs, ultimately amplifying their therapeutic potential. Given the crucial role ferroptosis plays in shaping the therapeutic outcomes of MSCs, we deem it imperative to further investigate the intricate interplay between programmed cell death and the therapeutic effectiveness of MSCs.
Collapse
Affiliation(s)
- Xin-Xing Wan
- Department of Endocrinology, Third Xiangya Hospital, Central South University, Changsha 410013, Hunan Province, China
| | - Xi-Min Hu
- Department of Dermatology, Xiangya Hospital, Central South University, Changsha 410008, Hunan Province, China
| | - Qi Zhang
- Department of Anatomy and Neurobiology, Central South University, Changsha 410000, Hunan Province, China
| | - Kun Xiong
- Department of Anatomy and Neurobiology, School of Basic Medical Science, Central South University, Changsha 410013, Hunan Province, China.
| |
Collapse
|
|
3
|
Liu Y, Cao Y, Li H, Liu H, Bi L, Chen Q, Peng R. A systematic review of microplastics emissions in kitchens: Understanding the links with diseases in daily life. ENVIRONMENT INTERNATIONAL 2024; 188:108740. [PMID: 38749117 DOI: 10.1016/j.envint.2024.108740] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 01/28/2024] [Revised: 04/14/2024] [Accepted: 05/09/2024] [Indexed: 06/11/2024]
Abstract
The intensification of microplastics (MPs) pollution has emerged as a formidable environmental challenge, with profound global implications. The pervasive presence of MPs across a multitude of environmental mediums, such as the atmosphere, soil, and oceans, extends to commonplace items, culminating in widespread human ingestion and accumulation via channels like food, water, and air. In the domestic realm, kitchens have become significant epicenters for MPs pollution. A plethora of kitchen utensils, encompassing coated non-stick pans, plastic cutting boards, and disposable utensils, are known to release substantial quantities of MPs particles in everyday use, which can then be ingested alongside food. This paper conducts a thorough examination of contemporary research addressing the release of MPs from kitchen utensils during usage and focuses on the health risks associated with MPs ingestion, as well as the myriad factors influencing the release of MPs in kitchen utensils. Leveraging the insights derived from this analysis, this paper proposes a series of strategic recommendations and measures targeted at mitigating the production of MPs in kitchen settings. These initiatives are designed not solely to diminish the release of MPs but also to enhance public awareness regarding this pressing environmental concern. By adopting more informed practices in kitchens, we can significantly contribute to the reduction of the environmental burden of MPs pollution, thus safeguarding both human health and the ecological system.
Collapse
Affiliation(s)
- Yinai Liu
- Institute of Life Sciences & Biomedicine Collaborative Innovation Center of Zhejiang Province, College of Life and Environmental Science, Wenzhou University, Wenzhou 325035, China
| | - Yu Cao
- Institute of Life Sciences & Biomedicine Collaborative Innovation Center of Zhejiang Province, College of Life and Environmental Science, Wenzhou University, Wenzhou 325035, China
| | - Huiqi Li
- Institute of Life Sciences & Biomedicine Collaborative Innovation Center of Zhejiang Province, College of Life and Environmental Science, Wenzhou University, Wenzhou 325035, China
| | - Huanpeng Liu
- Institute of Life Sciences & Biomedicine Collaborative Innovation Center of Zhejiang Province, College of Life and Environmental Science, Wenzhou University, Wenzhou 325035, China
| | - Liuliu Bi
- Institute of Life Sciences & Biomedicine Collaborative Innovation Center of Zhejiang Province, College of Life and Environmental Science, Wenzhou University, Wenzhou 325035, China
| | - Qianqian Chen
- Institute of Life Sciences & Biomedicine Collaborative Innovation Center of Zhejiang Province, College of Life and Environmental Science, Wenzhou University, Wenzhou 325035, China
| | - Renyi Peng
- Institute of Life Sciences & Biomedicine Collaborative Innovation Center of Zhejiang Province, College of Life and Environmental Science, Wenzhou University, Wenzhou 325035, China; Key Lab of Biohealth Materials and Chemistry of Wenzhou, Wenzhou University, Wenzhou 325035, China.
| |
Collapse
|
|
4
|
Mo Y, Mo L, Zhang Y, Zhang Y, Yuan J, Zhang Q. High glucose enhances the activation of NLRP3 inflammasome by ambient fine particulate matter in alveolar macrophages. Part Fibre Toxicol 2023; 20:41. [PMID: 37919797 PMCID: PMC10621103 DOI: 10.1186/s12989-023-00552-8] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/07/2023] [Accepted: 10/23/2023] [Indexed: 11/04/2023] Open
Abstract
BACKGROUND Epidemiological studies have demonstrated that individuals with preexisting conditions, including diabetes mellitus (DM), are more susceptible to air pollution. However, the underlying mechanisms remain unclear. In this study, we proposed that a high glucose setting enhances ambient fine particulate matter (PM2.5)-induced macrophage activation and secretion of the proinflammatory cytokine, IL-1β, through activation of the NLRP3 inflammasome, altering the balance between matrix metalloproteinases (MMPs) and tissue inhibitors of MMPs (TIMPs). RESULTS Exposure of mouse alveolar macrophages to non-cytotoxic doses of PM2.5 led to upregulation of IL-1β, activation of the NLRP3 inflammasome, increased nuclear translocation of the transcription factor NF-κB, increased generation of reactive oxygen species (ROS), and increased expression and enzymatic activity of MMP-9; these effects were enhanced when cells were pretreated with high glucose. However, pretreatment in a high glucose setting alone did not induce significant changes. ROS generation following PM2.5 exposure was abolished when cells were pretreated with ROS scavengers such as Trolox and superoxide dismutase (SOD), or with an NADPH oxidase inhibitor, DPI. Pretreatment of cells with DPI attenuated the effects of a high glucose setting on PM2.5-induced upregulation of IL-1β, activation of the NLRP3 inflammasome, and nuclear translocation of NF-κB. In addition, enhancement of PM2.5-induced expression and enzymatic activity of MMP-9 following high glucose pretreatment was not observed in primary alveolar macrophages obtained from NLRP3 or IL-1R1 knockout (KO) mice, where pro-IL-1β cannot be cleaved to IL-1β or cells are insensitive to IL-1β, respectively. CONCLUSIONS This study demonstrated that exposure of mouse alveolar macrophages to PM2.5 in a high glucose setting enhanced PM2.5-induced production of IL-1β through activation of the NLRP3 inflammasome and nuclear translocation of NF-κB due to PM2.5-induced oxidative stress, leading to MMP-9 upregulation. The key role of NADPH oxidase in PM2.5-induced ROS generation and activation of the IL-1β secretion pathway and the importance of IL-1β secretion and signaling in PM2.5-induced increases in MMP-9 enzymatic activity were also demonstrated. This study provides a further understanding of the potential mechanisms underlying the susceptibility of individuals with DM to air pollution and suggests potential therapeutic targets.
Collapse
Affiliation(s)
- Yiqun Mo
- Department of Epidemiology and Population Health, School of Public Health and Information Sciences, University of Louisville, 485 E. Gray Street, Louisville, KY, 40202, USA
| | - Luke Mo
- Department of Epidemiology and Population Health, School of Public Health and Information Sciences, University of Louisville, 485 E. Gray Street, Louisville, KY, 40202, USA
| | - Yue Zhang
- Northwestern University Feinberg School of Medicine, Chicago, IL, 60611, USA
| | - Yuanbao Zhang
- Department of Epidemiology and Population Health, School of Public Health and Information Sciences, University of Louisville, 485 E. Gray Street, Louisville, KY, 40202, USA
| | - Jiali Yuan
- Department of Epidemiology and Population Health, School of Public Health and Information Sciences, University of Louisville, 485 E. Gray Street, Louisville, KY, 40202, USA
| | - Qunwei Zhang
- Department of Epidemiology and Population Health, School of Public Health and Information Sciences, University of Louisville, 485 E. Gray Street, Louisville, KY, 40202, USA.
| |
Collapse
|
|
5
|
Mohamadi Y, Borhani-Haghighi M. TGN020 application against aquaporin 4 improved multiple sclerosis by inhibiting astrocytes, microglia, and NLRP3 inflammasome in a cuprizone mouse model. J Chem Neuroanat 2023; 132:102306. [PMID: 37394105 DOI: 10.1016/j.jchemneu.2023.102306] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/24/2023] [Revised: 06/20/2023] [Accepted: 06/30/2023] [Indexed: 07/04/2023]
Abstract
In multiple sclerosis (MS), activation of the astrocytes and microglia induces a cascading inflammatory response. Overexpression of the aquaporin 4 (AQP4) in the glia is a trigger for this reaction. This study aimed to block AQP4 by injecting TGN020 to alleviate the symptoms of MS. Total of 30 male mice were randomly divided into control (intact), cuprizone model of MS (fed with 0.2% cuprizone for 35 days), and TGN020-treated (received daily intraperitoneal injections of 200 mg/kg TGN020 with cuprizone intake) groups. Astrogliosis, M1-M2 microglia polarization, NLRP3 inflammasome activation, and demyelination were investigated in the corpus callosum by immunohistochemistry, real-time PCR, western blot, and luxol fast blue staining. The Rotarod test was performed for a behavior assessment. AQP4 inhibition caused a significant decrease in the expression of the astrocyte-specific marker, GFAP. It also changed the microglia polarization from M1 to M2 indicated by a significant downregulation of iNOS, CD86, MHC-ІІ, and upregulation of arginase1, CD206, and TREM-2. In addition, western blot data showed a significant decrease in the NLRP3, caspase1, and IL-1b proteins in the treatment group, which indicated inflammasome inactivation. The molecular changes following the TGN020 injection resulted in remyelination and motor recovery enhancement in the treatment group. In conclusion, the results draw the attention to the role of AQP4 in the cuprizone model of MS.
Collapse
Affiliation(s)
- Yousef Mohamadi
- Department of Anatomy, School of Medicine, Ilam University of Medical Sciences, Ilam, Iran
| | - Maryam Borhani-Haghighi
- Department of Anatomy, School of Medicine, Tehran University of Medical Sciences, Tehran, Iran.
| |
Collapse
|
|
6
|
Hojo M, Maeno A, Sakamoto Y, Yamamoto Y, Taquahashi Y, Hirose A, Suzuki J, Inomata A, Nakae D. Time-Course of Transcriptomic Change in the Lungs of F344 Rats Repeatedly Exposed to a Multiwalled Carbon Nanotube in a 2-Year Test. NANOMATERIALS (BASEL, SWITZERLAND) 2023; 13:2105. [PMID: 37513116 PMCID: PMC10383707 DOI: 10.3390/nano13142105] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Subscribe] [Scholar Register] [Received: 06/09/2023] [Revised: 07/13/2023] [Accepted: 07/17/2023] [Indexed: 07/30/2023]
Abstract
Despite intensive toxicological studies of carbon nanotubes (CNTs) over the last two decades, only a few studies have demonstrated their pulmonary carcinogenicities in chronic animal experiments, and the underlying molecular mechanisms are still unclear. To obtain molecular insights into CNT-induced lung carcinogenicity, we performed a transcriptomic analysis using a set of lung tissues collected from rats in a 2-year study, in which lung tumors were induced by repeated intratracheal instillations of a multiwalled carbon nanotube, MWNT-7. The RNA-seq-based transcriptome identified a large number of significantly differentially expressed genes at Year 0.5, Year 1, and Year 2. Ingenuity Pathway Analysis revealed that macrophage-elicited signaling pathways such as phagocytosis, acute phase response, and Toll-like receptor signaling were activated throughout the experimental period. At Year 2, cancer-related pathways including ERBB signaling and some axonal guidance signaling pathways such as EphB4 signaling were perturbed. qRT-PCR and immunohistochemistry indicated that several key molecules such as Osteopontin/Spp1, Hmox1, Mmp12, and ERBB2 were markedly altered and/or localized in the preneoplastic lesions, suggesting their participation in the induction of lung cancer. Our findings support a scenario of inflammation-induced carcinogenesis and contribute to a better understanding of the molecular mechanism of MWCNT carcinogenicity.
Collapse
Affiliation(s)
- Motoki Hojo
- Department of Pharmaceutical and Environmental Sciences, Tokyo Metropolitan Institute of Public Health, 3-24-1 Hyakunincho, Shinjuku-ku, Tokyo 169-0073, Japan
| | - Ai Maeno
- Department of Pharmaceutical and Environmental Sciences, Tokyo Metropolitan Institute of Public Health, 3-24-1 Hyakunincho, Shinjuku-ku, Tokyo 169-0073, Japan
| | - Yoshimitsu Sakamoto
- Department of Pharmaceutical and Environmental Sciences, Tokyo Metropolitan Institute of Public Health, 3-24-1 Hyakunincho, Shinjuku-ku, Tokyo 169-0073, Japan
| | - Yukio Yamamoto
- Department of Pharmaceutical and Environmental Sciences, Tokyo Metropolitan Institute of Public Health, 3-24-1 Hyakunincho, Shinjuku-ku, Tokyo 169-0073, Japan
| | - Yuhji Taquahashi
- Division of Cellular and Molecular Toxicology, Center for Biological Safety and Research, National Institute of Health Sciences, 3-25-26 Tono-machi, Kawasaki-ku, Kawasaki 210-9501, Kanagawa, Japan
| | - Akihiko Hirose
- Chemicals Assessment and Research Center, Chemicals Evaluation and Research Institute, Japan, 1-4-25 Koraku, Bunkyo-ku, Tokyo 112-0004, Japan
| | - Jin Suzuki
- Department of Pharmaceutical and Environmental Sciences, Tokyo Metropolitan Institute of Public Health, 3-24-1 Hyakunincho, Shinjuku-ku, Tokyo 169-0073, Japan
| | - Akiko Inomata
- Department of Pharmaceutical and Environmental Sciences, Tokyo Metropolitan Institute of Public Health, 3-24-1 Hyakunincho, Shinjuku-ku, Tokyo 169-0073, Japan
| | - Dai Nakae
- Department of Medical Sports, Faculty of Health Care and Medical Sports, Teikyo Heisei University, 4-1 Uruido-Minami, Ichihara 290-0193, Chiba, Japan
| |
Collapse
|
|
7
|
Pavan C, Santalucia R, Escolano-Casado G, Ugliengo P, Mino L, Turci F. Physico-Chemical Approaches to Investigate Surface Hydroxyls as Determinants of Molecular Initiating Events in Oxide Particle Toxicity. Int J Mol Sci 2023; 24:11482. [PMID: 37511241 PMCID: PMC10380507 DOI: 10.3390/ijms241411482] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/23/2023] [Revised: 07/04/2023] [Accepted: 07/11/2023] [Indexed: 07/30/2023] Open
Abstract
The study of molecular recognition patterns is crucial for understanding the interactions between inorganic (nano)particles and biomolecules. In this review we focus on hydroxyls (OH) exposed at the surface of oxide particles (OxPs) which can play a key role in molecular initiating events leading to OxPs toxicity. We discuss here the main analytical methods available to characterize surface OH from a quantitative and qualitative point of view, covering thermogravimetry, titration, ζ potential measurements, and spectroscopic approaches (NMR, XPS). The importance of modelling techniques (MD, DFT) for an atomistic description of the interactions between membranes/proteins and OxPs surfaces is also discussed. From this background, we distilled a new approach methodology (NAM) based on the combination of IR spectroscopy and bioanalytical assays to investigate the molecular interactions of OxPs with biomolecules and membranes. This NAM has been already successfully applied to SiO2 particles to identify the OH patterns responsible for the OxPs' toxicity and can be conceivably extended to other surface-hydroxylated oxides.
Collapse
Affiliation(s)
- Cristina Pavan
- Department of Chemistry, University of Torino, Via Giuria 7, 10125 Torino, Italy
- "G. Scansetti" Interdepartmental Centre for Studies on Asbestos and Other Toxic Particulates, University of Torino, 10125 Torino, Italy
- Louvain Centre for Toxicology and Applied Pharmacology, Université Catholique de Louvain, 1200 Brussels, Belgium
| | - Rosangela Santalucia
- Department of Chemistry, University of Torino, Via Giuria 7, 10125 Torino, Italy
- Nanostructured Interfaces and Surfaces (NIS) Interdepartmental Centre, University of Torino, 10125 Torino, Italy
| | - Guillermo Escolano-Casado
- Department of Chemistry, University of Torino, Via Giuria 7, 10125 Torino, Italy
- Nanostructured Interfaces and Surfaces (NIS) Interdepartmental Centre, University of Torino, 10125 Torino, Italy
| | - Piero Ugliengo
- Department of Chemistry, University of Torino, Via Giuria 7, 10125 Torino, Italy
- Nanostructured Interfaces and Surfaces (NIS) Interdepartmental Centre, University of Torino, 10125 Torino, Italy
| | - Lorenzo Mino
- Department of Chemistry, University of Torino, Via Giuria 7, 10125 Torino, Italy
- Nanostructured Interfaces and Surfaces (NIS) Interdepartmental Centre, University of Torino, 10125 Torino, Italy
| | - Francesco Turci
- Department of Chemistry, University of Torino, Via Giuria 7, 10125 Torino, Italy
- "G. Scansetti" Interdepartmental Centre for Studies on Asbestos and Other Toxic Particulates, University of Torino, 10125 Torino, Italy
- Nanostructured Interfaces and Surfaces (NIS) Interdepartmental Centre, University of Torino, 10125 Torino, Italy
| |
Collapse
|
|
8
|
Berkel C, Cacan E. Pollutant-induced pyroptosis in humans and other animals. Life Sci 2023; 316:121386. [PMID: 36657639 DOI: 10.1016/j.lfs.2023.121386] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/10/2022] [Revised: 01/06/2023] [Accepted: 01/08/2023] [Indexed: 01/19/2023]
Abstract
Pyroptosis is a form of lytic cell death with pro-inflammatory characteristics, induced upon the activation of certain inflammatory caspases by inflammasome complexes such as NLRP3 inflammasome. Gasdermin proteins as the mediators of pyroptosis form cell membrane pores upon activation, which release certain cellular contents into the extracellular space including inflammatory cytokines such as IL-1β and IL-18, and also damage the integrity of the cell membrane. Gasdermins have been implicated in autoimmune and inflammatory diseases, infectious diseases, deafness and cancer. Mostly in the last 2 years, diverse pollutant types including particulate matter, cadmium and polystyrene microplastics were reported to induce pyroptotic cell death in diverse tissues from mammals to birds. In the present study, we review our current understanding of pollutant-induced pyroptosis as well as current knowledge of upstream events leading to pyroptotic cell death upon exposure to pollutants.
Collapse
Affiliation(s)
- Caglar Berkel
- Department of Molecular Biology and Genetics, Tokat Gaziosmanpasa University, Tokat 60250, Turkey.
| | - Ercan Cacan
- Department of Molecular Biology and Genetics, Tokat Gaziosmanpasa University, Tokat 60250, Turkey.
| |
Collapse
|
|
9
|
Bredeck G, Busch M, Rossi A, Stahlmecke B, Fomba KW, Herrmann H, Schins RPF. Inhalable Saharan dust induces oxidative stress, NLRP3 inflammasome activation, and inflammatory cytokine release. ENVIRONMENT INTERNATIONAL 2023; 172:107732. [PMID: 36680803 DOI: 10.1016/j.envint.2023.107732] [Citation(s) in RCA: 12] [Impact Index Per Article: 6.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 06/24/2022] [Revised: 12/07/2022] [Accepted: 01/02/2023] [Indexed: 06/17/2023]
Abstract
Desert dust is increasingly recognized as a major air pollutant affecting respiratory health. Since desert dust exposure cannot be regulated, the hazardousness of its components must be understood to enable health risk mitigation strategies. Saharan dust (SD) comprises about half of the global desert dust and contains quartz, a toxic mineral dust that is known to cause severe lung diseases via oxidative stress and activation of the NLRP3 inflammasome-interleukin-1β pathway. We aimed to assess the physicochemical and microbial characteristics of SD responsible for toxic effects. Also, we studied the oxidative and pro-inflammatory potential of SD in alveolar epithelial cells and the activation of the NLRP3 inflammasome in macrophage-like cells in comparison to quartz dusts and synthetic amorphous silica (SAS). Characterization revealed that SD contained Fe, Al, trace metals, sulfate, diatomaceous earth, and endotoxin and had the capacity to generate hydroxyl radicals. We exposed A549 lung epithelial cells and wild-type and NLRP3-/- THP-1 macrophage-like cells to SD, three well-investigated quartz dusts, and SAS. SD induced oxidative stress in A549 cells after 24 h more potently than the quartz dusts. The quartz dusts and SAS upregulated interleukin 8 expression after 4 h and 24 h while SD only caused a transient upregulation. SD, the quartz dusts, and SAS induced interleukin-1β release from wild-type THP-1 cells>20-fold stronger than from NLRP3-/- THP-1 cells. Interleukin-1β release was lower for SD, in which microbial components including endotoxin were heat-destructed. In conclusion, microbial components in SD are pivotal for its toxicity. In the epithelium, the effects of SD contrasted with crystalline and amorphous silica in terms of potency and persistence. In macrophages, the strong involvement of the NLRP3 inflammasome emphasizes the acute and chronic health risks associated with desert dust exposure.
Collapse
Affiliation(s)
- Gerrit Bredeck
- IUF - Leibniz Research Institute for Environmental Medicine, Düsseldorf, Germany
| | - Mathias Busch
- IUF - Leibniz Research Institute for Environmental Medicine, Düsseldorf, Germany
| | - Andrea Rossi
- IUF - Leibniz Research Institute for Environmental Medicine, Düsseldorf, Germany
| | - Burkhard Stahlmecke
- Institute for Energy and Environmental Technology e.V. (IUTA), Duisburg, Germany
| | - Khanneh Wadinga Fomba
- Atmospheric Chemistry Department (ACD), Leibniz-Institute for Tropospheric Research (TROPOS), Leipzig, Germany
| | - Hartmut Herrmann
- Atmospheric Chemistry Department (ACD), Leibniz-Institute for Tropospheric Research (TROPOS), Leipzig, Germany
| | - Roel P F Schins
- IUF - Leibniz Research Institute for Environmental Medicine, Düsseldorf, Germany.
| |
Collapse
|
|
10
|
Wang X, Ren XM, He H, Li F, Liu K, Zhao F, Hu H, Zhang P, Huang B, Pan X. Cytotoxicity and pro-inflammatory effect of polystyrene nano-plastic and micro-plastic on RAW264.7 cells. Toxicology 2023; 484:153391. [PMID: 36503103 DOI: 10.1016/j.tox.2022.153391] [Citation(s) in RCA: 24] [Impact Index Per Article: 12.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/28/2022] [Revised: 11/25/2022] [Accepted: 12/06/2022] [Indexed: 12/13/2022]
Abstract
Numerous studies have shown that exposure to micro- or nano-plastics led to the cell viability and function of macrophages in the intestine tissue might be one possible mechanism. This study investigated the cytotoxicity and pro-inflammatory effect of 80 nm polystyrene-nano-plastic (PS-NP) and 3 µm PS-micro-plastic (PS-MP) on mouse macrophages RAW264.7 cells. Our results showed that exposure to PS-NP or PS-MP induced apoptosis of cells at 5 or 10 μg/mL, respectively. Besides, PS-NP enhanced the secretion of inflammatory cytokines (Tumor necrosis factor-α, Interleukin-6 and Interleukin-10) with the lowest effective concentration (LOEC) of 1, 0.01, and 0.01 μg/mL, respectively. PS-MP enhanced secretion of TNF-α and IL-10 with the LOEC of 1 and 0.01 μg/mL, respectively. We further studied the possible mechanisms of the effects of PS-NP or PS-MP on RAW264.7 cells. We found they might cause cytotoxicity and inflammatory effects by producing reactive oxygen species and nitric oxide in the cells. Accordingly, our results demonstrated that PS-NP and PS-MP had cytotoxicity and pro-inflammatory effect on macrophages, which might further lead to intestinal inflammation. Moreover, we revealed that the PS-NP had more potent adverse impacts on macrophages than PS-MP.
Collapse
Affiliation(s)
- Xiaoxia Wang
- Faculty of Environmental Science and Engineering, Kunming University of Science and Technology, Kunming 650500, China
| | - Xiao-Min Ren
- Faculty of Environmental Science and Engineering, Kunming University of Science and Technology, Kunming 650500, China.
| | - Huan He
- Faculty of Environmental Science and Engineering, Kunming University of Science and Technology, Kunming 650500, China
| | - Fan Li
- Faculty of Environmental Science and Engineering, Kunming University of Science and Technology, Kunming 650500, China
| | - Kunqian Liu
- Faculty of Environmental Science and Engineering, Kunming University of Science and Technology, Kunming 650500, China
| | - Fenqing Zhao
- Faculty of Environmental Science and Engineering, Kunming University of Science and Technology, Kunming 650500, China
| | - Huixiang Hu
- Faculty of Environmental Science and Engineering, Kunming University of Science and Technology, Kunming 650500, China
| | - Pingping Zhang
- Faculty of Environmental Science and Engineering, Kunming University of Science and Technology, Kunming 650500, China
| | - Bin Huang
- Faculty of Environmental Science and Engineering, Kunming University of Science and Technology, Kunming 650500, China; Yunnan Provincial Key Laboratory of Carbon Sequestration and Pollution Control in Soils, Kunming 650500, China
| | - Xuejun Pan
- Faculty of Environmental Science and Engineering, Kunming University of Science and Technology, Kunming 650500, China; Yunnan Provincial Key Laboratory of Carbon Sequestration and Pollution Control in Soils, Kunming 650500, China.
| |
Collapse
|
|
11
|
Han B, Liu Q, Su X, Zhou L, Zhang B, Kang H, Ning J, Li C, Zhao B, Niu Y, Chen W, Chen L, Zhang R. The role of PP2A /NLRP3 signaling pathway in ambient particulate matter 2.5 induced lung injury. CHEMOSPHERE 2022; 307:135794. [PMID: 35926746 DOI: 10.1016/j.chemosphere.2022.135794] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 02/24/2022] [Revised: 07/09/2022] [Accepted: 07/19/2022] [Indexed: 06/15/2023]
Abstract
Ambient particulate matter 2.5 (PM2.5) exposure has been linked to pulmonary fibrosis. However, the key signaling pathways remained unclear. In the present study, we applied a mouse model with myeloid-specific deletion of Ppp2r1a gene (encoding protein phosphatase 2 A (PP2A) A subunit) to identify the key signaling pathways involved in PM2.5-induced pulmonary fibrosis. PP2A Aα-/- homozygote mice and matched wild-type (WT) littermates were exposed to filtered air (FA), unfiltered air (UA), and concentrated PM2.5 (CA) in a real-ambient PM exposure system for 8 weeks and 16 weeks, respectively. The mice exposed to PM2.5 displayed a progressive inflammation and pulmonary fibrosis. Moreover, the expressions of NLRP3, pro-caspase-1, caspase-1, ASC and IL-1β were increased in mice lung following PM2.5 exposure, indicating PM2.5 exposure caused pulmonary inflammation by the NLRP3 pathways activation. Furthermore, the effects of PM exposure on pulmonary inflammation, pulmonary fibrosis, oxidative stress, and pulmonary function damage were significantly enhanced in PP2A-/- mice compared to WT mice, indicating the role of PP2A in the regulation of pulmonary injury induced by PM exposure. In vitro study confirmed that PP2A was involved in the PM2.5-induced inflammation response and NLRP3 inflammasome activation. Importantly, we identified PP2A regulated the activation of NLRP3 pathways by direct dephosphorylating IRE1α in response to PM2.5 exposure. Taken together, our results demonstrated that PP2A-IRE1α-NLRP3 signaling pathway played a crucial role in regulating the inflammation response, triggering the lung fibrogenesis upon PM2.5 exposure. Our findings provide new insights into regulatory role of PP2A in human diseases upon the PM exposure.
Collapse
Affiliation(s)
- Bin Han
- Department of Toxicology, Hebei Medical University, Shijiazhuang, 050017, Hebei, China.
| | - Qingping Liu
- Department of Toxicology, Hebei Medical University, Shijiazhuang, 050017, Hebei, China.
| | - Xuan Su
- Department of Toxicology, Hebei Medical University, Shijiazhuang, 050017, Hebei, China.
| | - Lixiao Zhou
- Department of Toxicology, Hebei Medical University, Shijiazhuang, 050017, Hebei, China.
| | - Boyuan Zhang
- Department of Toxicology, Hebei Medical University, Shijiazhuang, 050017, Hebei, China.
| | - Hui Kang
- Occupational Health and Environmental Health, Hebei Medical University, Shijiazhuang, 050017, Hebei, China.
| | - Jie Ning
- Department of Toxicology, Hebei Medical University, Shijiazhuang, 050017, Hebei, China.
| | - Chen Li
- Department of Toxicology, Hebei Medical University, Shijiazhuang, 050017, Hebei, China.
| | - Bo Zhao
- Department of Laboratory Diagnosis, Hebei Medical University, Shijiazhuang, 050017, Hebei, China.
| | - Yujie Niu
- Occupational Health and Environmental Health, Hebei Medical University, Shijiazhuang, 050017, Hebei, China; Hebei Key Laboratory of Environment and Human Health, Hebei Medical University, Shijiazhuang, 050017, Hebei, China.
| | - Wen Chen
- Department of Toxicology, School of Public Health, Sun Yat-sen University, Guangzhou, 510080, China.
| | - Liping Chen
- Department of Toxicology, School of Public Health, Sun Yat-sen University, Guangzhou, 510080, China.
| | - Rong Zhang
- Department of Toxicology, Hebei Medical University, Shijiazhuang, 050017, Hebei, China; Hebei Key Laboratory of Environment and Human Health, Hebei Medical University, Shijiazhuang, 050017, Hebei, China.
| |
Collapse
|
|
12
|
Noori M, Azimirad M, Eslami G, Looha MA, Yadegar A, Ghalavand Z, Zali MR. Surface layer protein A from hypervirulent Clostridioides difficile ribotypes induce significant changes in the gene expression of tight junctions and inflammatory response in human intestinal epithelial cells. BMC Microbiol 2022; 22:259. [PMID: 36303110 PMCID: PMC9608920 DOI: 10.1186/s12866-022-02665-0] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/19/2022] [Revised: 09/22/2022] [Accepted: 10/10/2022] [Indexed: 11/30/2022] Open
Abstract
BACKGROUND Surface layer protein A (SlpA), the primary outermost structure of Clostridioides difficile, plays an essential role in C. difficile pathogenesis, although its interaction with host intestinal cells are yet to be understood. The aim of this study was to investigate the effects of SlpA extracted from C. difficile on tight junction (TJ) proteins expression and induction of pro-inflammatory cytokines in human colon carcinoma cell line HT-29. SlpA was extracted from three toxigenic C. difficile clinical strains including RT126, RT001, RT084 as well as C. difficile ATCC 700057 as non-toxigenic strain. Cell viability was performed by MTT assay, and the mRNA expression of TJ proteins and inflammation-associated genes was determined using quantitative RT-PCR. Additionally, the secretion of IL-8, IL-1β and TNF-α cytokines was measured by ELISA. RESULTS C. difficile SlpA from selected RTs variably downregulated the expression level of TJs-assassinated genes and increased the expression level of TLR-4 and pro-inflammatory cytokines in HT-29 treated cells. SlpA from RT126 significantly (padj<0.05) decreased the gene expression level of claudins family and JAM-A and increased the secretion of IL-8, TNF-α and IL1-β as compared to untreated cells. Moreover, only SlpA from RT001 could significantly induce the expression of IL-6 (padj<0.05). CONCLUSION The results of the present study highlighted the importance of SlpA in the pathogenesis of CDI and C. difficile-induced inflammatory response in the gut. Further studies are required to unravel the significance of the observed results in promoting the intestinal inflammation and immune response induced by C. difficile SlpA from different RTs.
Collapse
Affiliation(s)
- Maryam Noori
- Department of Microbiology, School of Medicine, Shahid Beheshti University of Medical Sciences, Tehran, Iran
- Foodborne and Waterborne Diseases Research Center, Research Institute for Gastroenterology and Liver Diseases, Shahid Beheshti University of Medical Sciences, Tehran, Iran
| | - Masoumeh Azimirad
- Foodborne and Waterborne Diseases Research Center, Research Institute for Gastroenterology and Liver Diseases, Shahid Beheshti University of Medical Sciences, Tehran, Iran
| | - Gita Eslami
- Department of Microbiology, School of Medicine, Shahid Beheshti University of Medical Sciences, Tehran, Iran
| | - Mehdi Azizmohammad Looha
- Basic and Molecular Epidemiology of Gastrointestinal Disorders Research Center, Research Institute for Gastroenterology and Liver Diseases, Shahid Beheshti University of Medical Sciences, Tehran, Iran
| | - Abbas Yadegar
- Foodborne and Waterborne Diseases Research Center, Research Institute for Gastroenterology and Liver Diseases, Shahid Beheshti University of Medical Sciences, Tehran, Iran.
| | - Zohreh Ghalavand
- Department of Microbiology, School of Medicine, Shahid Beheshti University of Medical Sciences, Tehran, Iran.
| | - Mohammad Reza Zali
- Gastroenterology and Liver Diseases Research Center, Research Institute for Gastroenterology and Liver Diseases, Shahid Beheshti University of Medical Sciences, Tehran, Iran
| |
Collapse
|
|
13
|
Leinardi R, Longo Sanchez-Calero C, Huaux F. Think Beyond Particle Cytotoxicity: When Self-Cellular Components Released After Immunogenic Cell Death Explain Chronic Disease Development. FRONTIERS IN TOXICOLOGY 2022; 4:887228. [PMID: 35846433 PMCID: PMC9284505 DOI: 10.3389/ftox.2022.887228] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/01/2022] [Accepted: 06/13/2022] [Indexed: 11/13/2022] Open
Abstract
The prolonged perturbation of the immune system following the release of a plethora of self-molecules (known as damage-associated molecular patterns, DAMPs) by stressed or dying cells triggers acute and chronic pathological responses. DAMPs are commonly released after plasma membrane damage or complete rupture due to immunogenic cell death (ICD), upon numerous stressors including infectious and toxic agents. The set of DAMPs released after ICD include mature proinflammatory cytokines and alarmins, but also polymeric macromolecules. These self-intracellular components are recognized by injured and healthy surrounding cells via innate receptors, and induce upregulation of stress-response mechanisms, including inflammation. In this review, by overstepping the simple toxicological evaluation, we apply ICD and DAMP concepts to silica cytotoxicity, providing new insights on the mechanisms driving the progress and/or the exacerbation of certain SiO2–related pathologies. Finally, by proposing self-DNA as new crucial DAMP, we aim to pave the way for the development of innovative and easy-to-perform predictive tests to better identify the hazard of fine and ultrafine silica particles. Importantly, such mechanisms could be extended to nano/micro plastics and diesel particles, providing strategic advice and reports on their health issues.
Collapse
|
|
14
|
Campbell NV, Mickael C, Kumar S, Zhang H, Campbell IL, Gillen AE, Trentin CO, Diener K, Gao B, Kheyfets VO, Gu S, Kumar R, Phang T, Brown RD, Graham BB, Stenmark KR. Single-cell RNA sequencing and binary hierarchical clustering define lung interstitial macrophage heterogeneity in response to hypoxia. Am J Physiol Lung Cell Mol Physiol 2022; 323:L58-L68. [PMID: 35608266 PMCID: PMC9273277 DOI: 10.1152/ajplung.00104.2022] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/31/2022] [Revised: 05/13/2022] [Accepted: 05/15/2022] [Indexed: 11/22/2022] Open
Abstract
Few studies have examined lung interstitial macrophage (IM) molecular phenotypes after being exposed to hypoxia in vivo at the single-cell level, even though macrophages contribute to hypoxic pulmonary hypertension (PH). We aimed to determine IM diversity and its association with hypoxia-induced PH. We hypothesized that integrating single-cell RNA sequencing (scRNAseq) and binary hierarchal clustering (BHC) could resolve IM heterogeneity under normal homeostatic conditions and changes induced by hypoxia exposure. Cx3cr1GFP/+ reporter mice were exposed to normoxic conditions (∼21% [Formula: see text]) or exposed to 1 day (D1) or 7 days (D7) of hypoxia (∼10% [Formula: see text]). We used flow cytometry to isolate Cx3cr1+ IMs and the 10X Genomics platform for scRNAseq, Cell Ranger, Seurat, ClusterMap, monocle, ingenuity pathway analysis, and Fisher's exact test (q value < 0.05) for functional investigations. n = 374 (normoxia), n = 2,526 (D1), and n = 1,211 (D7) IMs were included in the analyses. We identified three normoxia-related cell types, five hypoxia-associated cell types that emerged at D1, and three that appeared at D7. We describe the existence of a putative resident trained innate IM, which is present in normoxia, transiently depleted at D1, and recovered after 7 days of sustained hypoxia. We also define a rare putative pathogenic population associated with transcripts implicated in PH development that emerges at D7. In closing, we describe the successful integration of BHC with scRNAseq to determine IM heterogeneity and its association with PH. These results shed light on how resident-trained innate IMs become more heterogeneous but ultimately accustomed to hypoxia.
Collapse
Affiliation(s)
- Nzali V Campbell
- Department of Pediatrics, University of Colorado, Anschutz Medical Campus, Aurora, Colorado
- Department of Medicine, University of Colorado, Anschutz Medical Campus, Aurora, Colorado
| | - Claudia Mickael
- Department of Medicine-Pulmonary Sciences & Critical Care, University of Colorado, Anschutz Medical Campus, Aurora, Colorado
| | - Sushil Kumar
- Department of Pediatrics, University of Colorado, Anschutz Medical Campus, Aurora, Colorado
- Department of Medicine, University of Colorado, Anschutz Medical Campus, Aurora, Colorado
| | - Hui Zhang
- Department of Pediatrics, University of Colorado, Anschutz Medical Campus, Aurora, Colorado
- Department of Medicine, University of Colorado, Anschutz Medical Campus, Aurora, Colorado
| | - Ian L Campbell
- School of Humanities and Science, Stanford University, Stanford, California
| | - Austin E Gillen
- Division of Hematology, Department of Medicine, University of Colorado Anschutz Medical Campus, Aurora, Colorado
| | - Caio O Trentin
- Department of Medicine-Pulmonary Sciences & Critical Care, University of Colorado, Anschutz Medical Campus, Aurora, Colorado
| | - Katrina Diener
- Department of Medicine-Pulmonary Sciences & Critical Care, University of Colorado, Anschutz Medical Campus, Aurora, Colorado
| | - Bifeng Gao
- Department of Medicine-Pulmonary Sciences & Critical Care, University of Colorado, Anschutz Medical Campus, Aurora, Colorado
| | - Vitaly O Kheyfets
- Department of Pediatrics, University of Colorado, Anschutz Medical Campus, Aurora, Colorado
- Department of Medicine, University of Colorado, Anschutz Medical Campus, Aurora, Colorado
| | - Sue Gu
- Department of Medicine-Pulmonary Sciences & Critical Care, University of Colorado, Anschutz Medical Campus, Aurora, Colorado
| | - Rahul Kumar
- Division of Hematology, Department of Medicine, University of Colorado Anschutz Medical Campus, Aurora, Colorado
| | - Tzu Phang
- Department of Medicine, University of Colorado, Anschutz Medical Campus, Aurora, Colorado
- Department of Medicine-Bioinformatics, University of Colorado, Anschutz Medical Campus, Aurora, Colorado
| | - R Dale Brown
- Department of Pediatrics, University of Colorado, Anschutz Medical Campus, Aurora, Colorado
- Department of Medicine, University of Colorado, Anschutz Medical Campus, Aurora, Colorado
| | - Brian B Graham
- Department of Medicine, University of California, San Francisco, California
| | - Kurt R Stenmark
- Department of Pediatrics, University of Colorado, Anschutz Medical Campus, Aurora, Colorado
- Department of Medicine, University of Colorado, Anschutz Medical Campus, Aurora, Colorado
| |
Collapse
|
|
15
|
Naguib M, Mekkawy IA, Mahmoud UM, Sayed AEDH. Genotoxic evaluation of silver nanoparticles in catfish Clarias gariepinus erythrocytes; DNA strand breakage using comet assay. SCIENTIFIC AFRICAN 2022; 16:e01260. [DOI: 10.1016/j.sciaf.2022.e01260] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/25/2022] Open
|
|
16
|
Gupta SS, Singh KP, Gupta S, Dusinska M, Rahman Q. Do Carbon Nanotubes and Asbestos Fibers Exhibit Common Toxicity Mechanisms? NANOMATERIALS 2022; 12:nano12101708. [PMID: 35630938 PMCID: PMC9145953 DOI: 10.3390/nano12101708] [Citation(s) in RCA: 8] [Impact Index Per Article: 2.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 04/08/2022] [Revised: 05/05/2022] [Accepted: 05/06/2022] [Indexed: 01/27/2023]
Abstract
During the last two decades several nanoscale materials were engineered for industrial and medical applications. Among them carbon nanotubes (CNTs) are the most exploited nanomaterials with global production of around 1000 tons/year. Besides several commercial benefits of CNTs, the fiber-like structures and their bio-persistency in lung tissues raise serious concerns about the possible adverse human health effects resembling those of asbestos fibers. In this review, we present a comparative analysis between CNTs and asbestos fibers using the following four parameters: (1) fibrous needle-like shape, (2) bio-persistent nature, (3) high surface to volume ratio and (4) capacity to adsorb toxicants/pollutants on the surface. We also compare mechanisms underlying the toxicity caused by certain diameters and lengths of CNTs and asbestos fibers using downstream pathways associated with altered gene expression data from both asbestos and CNT exposure. Our results suggest that indeed certain types of CNTs are emulating asbestos fiber as far as associated toxicity is concerned.
Collapse
Affiliation(s)
- Suchi Smita Gupta
- Department of Systems Biology and Bioinformatics, University of Rostock, 18051 Rostock, Germany; (S.S.G.); (K.P.S.); (S.G.)
| | - Krishna P. Singh
- Department of Systems Biology and Bioinformatics, University of Rostock, 18051 Rostock, Germany; (S.S.G.); (K.P.S.); (S.G.)
| | - Shailendra Gupta
- Department of Systems Biology and Bioinformatics, University of Rostock, 18051 Rostock, Germany; (S.S.G.); (K.P.S.); (S.G.)
| | - Maria Dusinska
- Health Effects Laboratory, Department of Environmental Chemistry, NILU-Norwegian Institute for Air Research, 2007 Kjeller, Norway;
| | - Qamar Rahman
- Amity Institute of Biotechnology, Amity University, Lucknow 226028, India
- Correspondence:
| |
Collapse
|
|
17
|
Lučiūnaitė A, Dalgėdienė I, Žilionis R, Mašalaitė K, Norkienė M, Šinkūnas A, Gedvilaitė A, Kučinskaitė-Kodzė I, Žvirblienė A. Activation of NLRP3 Inflammasome by Virus-Like Particles of Human Polyomaviruses in Macrophages. Front Immunol 2022; 13:831815. [PMID: 35355981 PMCID: PMC8959312 DOI: 10.3389/fimmu.2022.831815] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/08/2021] [Accepted: 02/08/2022] [Indexed: 11/21/2022] Open
Abstract
Viral antigens can activate phagocytes, inducing inflammation, but the mechanisms are barely explored. The aim of this study is to investigate how viral oligomeric proteins of different structures induce inflammatory response in macrophages. Human THP-1 cell line was used to prepare macrophages that were treated with filamentous nucleocapsid-like particles (NLPs) of paramyxoviruses and spherical virus-like particles (VLPs) of human polyomaviruses. The effects of viral proteins on cell viability, pro-inflammatory cytokines’ production, and NLRP3 inflammasome activation were investigated. Filamentous NLPs did not induce inflammation while spherical VLPs mediated inflammatory response followed by NLRP3 inflammasome activation. Inhibitors of cathepsins and K+ efflux decreased IL-1β release and cell death, indicating a complex inflammasome activation process. A similar activation pattern was observed in primary human macrophages. Single-cell RNAseq analysis of THP-1 cells revealed several cell activation states different in inflammation-related genes. This study provides new insights into the interaction of viral proteins with immune cells and suggests that structural properties of oligomeric proteins may define cell activation pathways.
Collapse
Affiliation(s)
- Asta Lučiūnaitė
- Institute of Biotechnology, Life Sciences Center, Vilnius University, Vilnius, Lithuania
| | - Indrė Dalgėdienė
- Institute of Biotechnology, Life Sciences Center, Vilnius University, Vilnius, Lithuania
| | - Rapolas Žilionis
- Institute of Biotechnology, Life Sciences Center, Vilnius University, Vilnius, Lithuania.,R&D Department, Droplet Genomics, Vilnius, Lithuania
| | - Kristina Mašalaitė
- Institute of Biotechnology, Life Sciences Center, Vilnius University, Vilnius, Lithuania
| | - Milda Norkienė
- Institute of Biotechnology, Life Sciences Center, Vilnius University, Vilnius, Lithuania
| | | | - Alma Gedvilaitė
- Institute of Biotechnology, Life Sciences Center, Vilnius University, Vilnius, Lithuania
| | | | - Aurelija Žvirblienė
- Institute of Biotechnology, Life Sciences Center, Vilnius University, Vilnius, Lithuania
| |
Collapse
|
|
18
|
Lam M, Mansell A, Tate MD. Another One Fights the Dust - Targeting the NLRP3 Inflammasome for the Treatment of Silicosis. Am J Respir Cell Mol Biol 2022; 66:601-611. [PMID: 35290170 DOI: 10.1165/rcmb.2021-0545tr] [Citation(s) in RCA: 12] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/24/2022] Open
Abstract
Silicosis is a multifaceted lung disease, characterised by persistent inflammation and structural remodelling. Despite its poor prognosis, there are no treatments currently available for patients with silicosis. Recent pre-clinical findings in models of lung fibrosis have suggested a major role for the nucleotide binding domain and leucine-rich repeat pyrin domain containing 3 (NLRP3) inflammasome in silica-driven inflammation and fibrosis. This review outlines the beneficial effects of targeting the NLRP3 inflammasome in in vitro cell experiments and in in vivo animal models, whereby inflammation and fibrosis are abrogated following NLRP3 inflammasome inhibition. While preclinical evidence is promising, studies which explore NLRP3 inflammasomes in the clinical setting are warranted. In particular, there is still a need to identify biomarkers which may be helpful for the early detection of silicosis and to fully elucidate mechanisms underlying these beneficial effects to further develop or repurpose existing anti-NLRP3 drugs as novel treatments that limit disease progression.
Collapse
Affiliation(s)
- Maggie Lam
- Hudson Institute of Medical Research Centre for Innate Immunity and Infectious Diseases, 366840, Clayton, Victoria, Australia.,Monash University , Department of Molecular and Translational Sciences, Clayton, Victoria, Australia
| | - Ashley Mansell
- Hudson Institute of Medical Research Centre for Innate Immunity and Infectious Diseases, 366840, Clayton, Victoria, Australia.,Monash Univerisity, Department of Molecular and Translational Sciences, Clayton, Victoria, Australia.,Adiso Therapeutics Inc, Concord, Massachusetts, United States
| | - Michelle D Tate
- Hudson Institute of Medical Research Centre for Innate Immunity and Infectious Diseases, 366840, Clayton, Victoria, Australia.,Monash University, Department of Molecular and Translational Sciences, Clayton, Victoria, Australia;
| |
Collapse
|
|
19
|
Lynch RI, Lavelle EC. Immuno-modulatory biomaterials as anti-inflammatory therapeutics. Biochem Pharmacol 2022; 197:114890. [PMID: 34990595 DOI: 10.1016/j.bcp.2021.114890] [Citation(s) in RCA: 14] [Impact Index Per Article: 4.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/16/2021] [Revised: 12/07/2021] [Accepted: 12/07/2021] [Indexed: 12/16/2022]
Abstract
Biocompatible and biodegradable biomaterials are used extensively in regenerative medicine and serve as a tool for tissue replacement, as a platform for regeneration of injured tissue, and as a vehicle for delivery of drugs. One of the key factors that must be addressed in developing successful biomaterial-based therapeutics is inflammation. Whilst inflammation is initially essential for wound healing; bringing about clearance of debris and infection, prolonged inflammation can result in delayed wound healing, rejection of the biomaterial, further tissue damage and increased scarring and fibrosis. In this context, the choice of biomaterial must be considered carefully to minimise further induction of inflammation. Here we address the ability of the biomaterials themselves to modulate inflammatory responses and outline how the physico-chemical properties of the materials impact on their pro and anti-inflammatory properties (Fig. 1).
Collapse
Affiliation(s)
- Roisin I Lynch
- Adjuvant Research Group, School of Biochemistry and Immunology, Trinity Biomedical Sciences Institute, Trinity College Dublin, D02R590, Dublin 2, Ireland
| | - Ed C Lavelle
- Adjuvant Research Group, School of Biochemistry and Immunology, Trinity Biomedical Sciences Institute, Trinity College Dublin, D02R590, Dublin 2, Ireland.
| |
Collapse
|
|
20
|
Favor OK, Pestka JJ, Bates MA, Lee KSS. Centrality of Myeloid-Lineage Phagocytes in Particle-Triggered Inflammation and Autoimmunity. FRONTIERS IN TOXICOLOGY 2021; 3:777768. [PMID: 35295146 PMCID: PMC8915915 DOI: 10.3389/ftox.2021.777768] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/15/2021] [Accepted: 10/19/2021] [Indexed: 12/14/2022] Open
Abstract
Exposure to exogenous particles found as airborne contaminants or endogenous particles that form by crystallization of certain nutrients can activate inflammatory pathways and potentially accelerate autoimmunity onset and progression in genetically predisposed individuals. The first line of innate immunological defense against particles are myeloid-lineage phagocytes, namely macrophages and neutrophils, which recognize/internalize the particles, release inflammatory mediators, undergo programmed/unprogrammed death, and recruit/activate other leukocytes to clear the particles and resolve inflammation. However, immunogenic cell death and release of damage-associated molecules, collectively referred to as "danger signals," coupled with failure to efficiently clear dead/dying cells, can elicit unresolved inflammation, accumulation of self-antigens, and adaptive leukocyte recruitment/activation. Collectively, these events can promote loss of immunological self-tolerance and onset/progression of autoimmunity. This review discusses critical molecular mechanisms by which exogenous particles (i.e., silica, asbestos, carbon nanotubes, titanium dioxide, aluminum-containing salts) and endogenous particles (i.e., monosodium urate, cholesterol crystals, calcium-containing salts) may promote unresolved inflammation and autoimmunity by inducing toxic responses in myeloid-lineage phagocytes with emphases on inflammasome activation and necrotic and programmed cell death pathways. A prototypical example is occupational exposure to respirable crystalline silica, which is etiologically linked to systemic lupus erythematosus (SLE) and other human autoimmune diseases. Importantly, airway instillation of SLE-prone mice with crystalline silica elicits severe pulmonary pathology involving accumulation of particle-laden alveolar macrophages, dying and dead cells, nuclear and cytoplasmic debris, and neutrophilic inflammation that drive cytokine, chemokine, and interferon-regulated gene expression. Silica-induced immunogenic cell death and danger signal release triggers accumulation of T and B cells, along with IgG-secreting plasma cells, indicative of ectopic lymphoid tissue neogenesis, and broad-spectrum autoantibody production in the lung. These events drive early autoimmunity onset and accelerate end-stage autoimmune glomerulonephritis. Intriguingly, dietary supplementation with ω-3 fatty acids have been demonstrated to be an intervention against silica-triggered murine autoimmunity. Taken together, further insight into how particles drive immunogenic cell death and danger signaling in myeloid-lineage phagocytes and how these responses are influenced by the genome will be essential for identification of novel interventions for preventing and treating inflammatory and autoimmune diseases associated with these agents.
Collapse
Affiliation(s)
- Olivia K. Favor
- Department of Pharmacology and Toxicology, College of Osteopathic Medicine, Michigan State University, East Lansing, MI, United States
- Institute for Integrative Toxicology, Michigan State University, East Lansing, MI, United States
| | - James J. Pestka
- Institute for Integrative Toxicology, Michigan State University, East Lansing, MI, United States
- Department of Food Science and Human Nutrition, Michigan State University, East Lansing, MI, United States
- Department of Microbiology and Molecular Genetics, Michigan State University, East Lansing, MI, United States
| | - Melissa A. Bates
- Institute for Integrative Toxicology, Michigan State University, East Lansing, MI, United States
- Department of Food Science and Human Nutrition, Michigan State University, East Lansing, MI, United States
| | - Kin Sing Stephen Lee
- Department of Pharmacology and Toxicology, College of Osteopathic Medicine, Michigan State University, East Lansing, MI, United States
- Institute for Integrative Toxicology, Michigan State University, East Lansing, MI, United States
- Department of Chemistry, Michigan State University, East Lansing, MI, United States
| |
Collapse
|
|
21
|
Nandi D, Shivrayan M, Gao J, Krishna J, Das R, Liu B, Thanyumanavan S, Kulkarni A. Core Hydrophobicity of Supramolecular Nanoparticles Induces NLRP3 Inflammasome Activation. ACS APPLIED MATERIALS & INTERFACES 2021; 13:45300-45314. [PMID: 34543013 PMCID: PMC8761361 DOI: 10.1021/acsami.1c14082] [Citation(s) in RCA: 13] [Impact Index Per Article: 3.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 06/13/2023]
Abstract
Designer nanomaterials capable of delivering immunomodulators to specific immune cells have been extensively studied. However, emerging evidence suggests that several of these nanomaterials can nonspecifically activate NLRP3 inflammasomes, an intracellular multiprotein complex controlling various immune cell functions, leading to undesirable effects. To understand what nanoparticle attributes activate inflammasomes, we designed a multiparametric polymer supramolecular nanoparticle system to modulate various surface and core nanoparticle-associated molecular patterns (NAMPs), one at a time. We also investigated several underlying signaling pathways, including lysosomal rupture-cathepsin B maturation and calcium flux-mitochondrial ROS production, to gain mechanistic insights into NAMPs-mediated inflammasome activation. Here, we report that out of the four NAMPs tested, core hydrophobicity strongly activates and positively correlates with the NLRP3 assembly compared to surface charge, core rigidity, and surface hydrophobicity. Moreover, we demonstrate different signaling inclinations and kinetics followed by differential core hydrophobicity patterns with the most hydrophobic ones exhibiting both lysosomal rupture and calcium influx early on. Altogether, this study will help design the next generation of polymeric nanomaterials for specific regulation of inflammasome activation, aiding efficient immunotherapy and vaccine delivery.
Collapse
Affiliation(s)
- Dipika Nandi
- Department of Chemical Engineering, University of Massachusetts, Amherst, Massachusetts 01003, USA
- Department of Veterinary and Animal Sciences, University of Massachusetts, Amherst, Massachusetts 01003, USA
| | - Manisha Shivrayan
- Department of Chemistry, University of Massachusetts, Amherst, Massachusetts 01003, USA
| | - Jingjing Gao
- Department of Chemistry, University of Massachusetts, Amherst, Massachusetts 01003, USA
| | - Jithu Krishna
- Department of Chemistry, University of Massachusetts, Amherst, Massachusetts 01003, USA
| | - Ritam Das
- Department of Chemistry, University of Massachusetts, Amherst, Massachusetts 01003, USA
| | - Bin Liu
- Department of Chemistry, University of Massachusetts, Amherst, Massachusetts 01003, USA
- Department of Chemistry, Massachusetts Institute of Technology, Cambridge, Massachusetts, 02139, USA
| | - S. Thanyumanavan
- Department of Chemistry, University of Massachusetts, Amherst, Massachusetts 01003, USA
- Department of Biomedical Engineering, University of Massachusetts, Amherst, Massachusetts, 01003, USA
- Center for Bioactive Delivery, Institute for Applied Life Sciences, University of Massachusetts, Amherst, Massachusetts 01003, USA
| | - Ashish Kulkarni
- Department of Chemical Engineering, University of Massachusetts, Amherst, Massachusetts 01003, USA
- Department of Veterinary and Animal Sciences, University of Massachusetts, Amherst, Massachusetts 01003, USA
- Department of Chemistry, University of Massachusetts, Amherst, Massachusetts 01003, USA
- Department of Biomedical Engineering, University of Massachusetts, Amherst, Massachusetts, 01003, USA
- Center for Bioactive Delivery, Institute for Applied Life Sciences, University of Massachusetts, Amherst, Massachusetts 01003, USA
| |
Collapse
|
|
22
|
Orsi M, Palmai-Pallag M, Yakoub Y, Ibouraadaten S, De Beukelaer M, Bouzin C, Bearzatto B, Ambroise J, Gala JL, Brusa D, Lison D, Huaux F. Monocytic Ontogeny of Regenerated Macrophages Characterizes the Mesotheliomagenic Responses to Carbon Nanotubes. Front Immunol 2021; 12:666107. [PMID: 34194430 PMCID: PMC8236701 DOI: 10.3389/fimmu.2021.666107] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/26/2021] [Accepted: 05/28/2021] [Indexed: 12/13/2022] Open
Abstract
Macrophages are not only derived from circulating blood monocytes or embryonic precursors but also expand by proliferation. The origin determines macrophage fate and functions in steady state and pathological conditions. Macrophages predominantly infiltrate fibre-induced mesothelioma tumors and contribute to cancer development. Here, we revealed their ontogeny by comparing the response to needle-like mesotheliomagenic carbon nanotubes (CNT-7) with tangled-like non-mesotheliomagenic CNT-T. In a rat peritoneal cavity model of mesothelioma, both CNT induced a rapid macrophage disappearance reaction (MDR) of MHCIIlow resident macrophages generating an empty niche available for macrophage repopulation. Macrophage depletion after mesotheliomagenic CNT-7 was followed by a substantial inflammatory reaction, and macrophage replenishment completed after 7 days. Thirty days after non-mesotheliomagenic CNT-T, macrophage repopulation was still incomplete and accompanied by a limited inflammatory reaction. Cell depletion experiments, flow cytometry and RNA-seq analysis demonstrated that, after mesotheliomagenic CNT-7 exposure, resident macrophages were mainly replaced by an influx of monocytes, which differentiated locally into MHCIIhigh inflammatory macrophages. In contrast, the low inflammatory response induced by CNT-T was associated by the accumulation of self-renewing MHCIIlow macrophages that initially derive from monocytes. In conclusion, the mesotheliomagenic response to CNT specifically relies on macrophage niche recolonization by monocyte-derived inflammatory macrophages. In contrast, the apparent homeostasis after non-mesotheliomagenic CNT treatment involves a macrophage regeneration by proliferation. Macrophage depletion and repopulation are thus decisive events characterizing the carcinogenic activity of particles and fibres.
Collapse
Affiliation(s)
- Micaela Orsi
- Louvain Centre for Toxicology and Applied Pharmacology (LTAP), Institute of Experimental and Clinical Research (IREC), Université Catholique de Louvain (UCLouvain), Brussels, Belgium
| | - Mihaly Palmai-Pallag
- Louvain Centre for Toxicology and Applied Pharmacology (LTAP), Institute of Experimental and Clinical Research (IREC), Université Catholique de Louvain (UCLouvain), Brussels, Belgium
| | - Yousof Yakoub
- Louvain Centre for Toxicology and Applied Pharmacology (LTAP), Institute of Experimental and Clinical Research (IREC), Université Catholique de Louvain (UCLouvain), Brussels, Belgium
| | - Saloua Ibouraadaten
- Louvain Centre for Toxicology and Applied Pharmacology (LTAP), Institute of Experimental and Clinical Research (IREC), Université Catholique de Louvain (UCLouvain), Brussels, Belgium
| | - Michèle De Beukelaer
- Imaging Platform, Institute of Experimental and Clinical Research (IREC), Université Catholique de Louvain (UCLouvain), Brussels, Belgium
| | - Caroline Bouzin
- Imaging Platform, Institute of Experimental and Clinical Research (IREC), Université Catholique de Louvain (UCLouvain), Brussels, Belgium
| | - Bertrand Bearzatto
- Center for Applied Molecular Technologies, Institute of Experimental and Clinical Research (IREC), Cliniques Universitaires Saint-Luc and Université Catholique de Louvain (UCLouvain), Brussels, Belgium
| | - Jérôme Ambroise
- Center for Applied Molecular Technologies, Institute of Experimental and Clinical Research (IREC), Cliniques Universitaires Saint-Luc and Université Catholique de Louvain (UCLouvain), Brussels, Belgium
| | - Jean-Luc Gala
- Center for Applied Molecular Technologies, Institute of Experimental and Clinical Research (IREC), Cliniques Universitaires Saint-Luc and Université Catholique de Louvain (UCLouvain), Brussels, Belgium
| | - Davide Brusa
- Flow Cytometry Platform, Institute of Experimental and Clinical Research (IREC), Université Catholique de Louvain (UCLouvain), Brussels, Belgium
| | - Dominique Lison
- Louvain Centre for Toxicology and Applied Pharmacology (LTAP), Institute of Experimental and Clinical Research (IREC), Université Catholique de Louvain (UCLouvain), Brussels, Belgium
| | - François Huaux
- Louvain Centre for Toxicology and Applied Pharmacology (LTAP), Institute of Experimental and Clinical Research (IREC), Université Catholique de Louvain (UCLouvain), Brussels, Belgium
| |
Collapse
|
|
23
|
High-mobility group box protein-1 induces acute pancreatitis through activation of neutrophil extracellular trap and subsequent production of IL-1β. Life Sci 2021; 286:119231. [PMID: 33600865 DOI: 10.1016/j.lfs.2021.119231] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/06/2020] [Revised: 02/01/2021] [Accepted: 02/10/2021] [Indexed: 12/22/2022]
Abstract
PURPOSE The aim of this study is to evaluate acute pancreatitis (AP)-associated NET activation mediated by a novel inflammatory mediator (high-mobility group box protein-1 [HMGB1]) and proinflammatory cytokine responses. METHODS In this study, primary neutrophils, monocytes, and monocytic cell line Thp-1-derived macrophages were isolated and treated with HMGB1, lipopolysaccharide (LPS), adenosine triphosphate (ATP), and ATP + ATP inhibitor. The effects of HMGB1, ATP, and deoxyribonuclease (DNAse) were then examined for their in vivo effects using a newly established AP mouse model. RESULTS The mRNA and protein levels of inflammasome and interleukin IL-1β in cells, blood, and pancreatic tissues were examined. Within-cell nuclear DNA signal, cell-free DNA concentration, and pancreatic tissue damage were investigated. Our study showed that HMGB1 triggers NET formation in neutrophils and promotes the activation of inflammasome complexes (the NLR family, pyrin domain containing 3, and NLRP3; ASC; and caspase-1); therefore, the production of IL-1β is induced in human monocytes/macrophages. HMGB1 and NET cooperatively stimulate IL-1β processing in macrophages. Furthermore, the AP mouse model confirmed these HMGB1-mediated molecular mechanisms in vivo and indicated that HMGB1 is required for NET activation. CONCLUSIONS We found that NET inhibition reverses HMGB1-stimulated inflammasome activation and IL-1β production. HMGB1 thus leads to pancreatic injury through the activation of NET and subsequently induces IL-1β processing from neutrophils to pancreatic tissues. These findings demonstrate that HMGB1 and NET are new therapeutic targets for inflammation suppression in severe AP.
Collapse
|
|
24
|
Baranov MV, Kumar M, Sacanna S, Thutupalli S, van den Bogaart G. Modulation of Immune Responses by Particle Size and Shape. Front Immunol 2021; 11:607945. [PMID: 33679696 PMCID: PMC7927956 DOI: 10.3389/fimmu.2020.607945] [Citation(s) in RCA: 141] [Impact Index Per Article: 35.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/18/2020] [Accepted: 12/23/2020] [Indexed: 12/12/2022] Open
Abstract
The immune system has to cope with a wide range of irregularly shaped pathogens that can actively move (e.g., by flagella) and also dynamically remodel their shape (e.g., transition from yeast-shaped to hyphal fungi). The goal of this review is to draw general conclusions of how the size and geometry of a pathogen affect its uptake and processing by phagocytes of the immune system. We compared both theoretical and experimental studies with different cells, model particles, and pathogenic microbes (particularly fungi) showing that particle size, shape, rigidity, and surface roughness are important parameters for cellular uptake and subsequent immune responses, particularly inflammasome activation and T cell activation. Understanding how the physical properties of particles affect immune responses can aid the design of better vaccines.
Collapse
Affiliation(s)
- Maksim V. Baranov
- Department of Molecular Immunology and Microbiology, Groningen Biomolecular Sciences and Biotechnology Institute, University of Groningen, Groningen, Netherlands
| | - Manoj Kumar
- Simons Center for the Study of Living Machines, National Centre for Biological Sciences, Tata Institute for Fundamental Research, Bangalore, India
| | - Stefano Sacanna
- Molecular Design Institute, Department of Chemistry, New York University, New York, NY, United States
| | - Shashi Thutupalli
- Simons Center for the Study of Living Machines, National Centre for Biological Sciences, Tata Institute for Fundamental Research, Bangalore, India
- International Centre for Theoretical Sciences, Tata Institute for Fundamental Research, Bangalore, India
| | - Geert van den Bogaart
- Department of Molecular Immunology and Microbiology, Groningen Biomolecular Sciences and Biotechnology Institute, University of Groningen, Groningen, Netherlands
| |
Collapse
|
|
25
|
De Rentiis AMA, Pink M, Verma N, Schmitz-Spanke S. Assessment of the different skin sensitization potentials of irritants and allergens as single substances and in combination using the KeratinoSens assay. Contact Dermatitis 2021; 84:317-325. [PMID: 33320367 DOI: 10.1111/cod.13762] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/20/2020] [Revised: 12/07/2020] [Accepted: 12/10/2020] [Indexed: 11/27/2022]
Abstract
BACKGROUND People are exposed to mixtures containing allergens and irritants often causing contact dermatitis. Therefore, regulatory authorities require systematic information on the effects of mixtures on the sensitization threshold. In this study a moderate (cinnamal) and a weak (ethylene glycol dimethacrylate) allergen were combined with irritants covering different mechanisms of action (sodium dodecyl sulfate, salicylic acid, and α-pinene). For a systematic approach, the single substances were initially tested using the KeratinoSens assay. Thereafter, each allergen was combined with noncytotoxic concentrations of the irritants. METHOD The KeratinoSens assay was applied for the single substances according to OECD (Organisation for Economic Co-operation and Development) Test Guideline 442D. Based on these results, three noncytotoxic concentrations of the irritants were selected and applied simultaneously with 12 concentrations of the allergens to the KeratinoSens cells. Sensitization threshold and cytotoxicity were measured and compared with the individual testing. RESULTS The combinations of allergens and irritants differed from the effects of the single substances and lowered the sensitization threshold. The quantitative approach allowed a clear description of the changes which varied by factors between 1.1 and 10.3. CONCLUSIONS Overall, the allergen was the prominent compound in the mixture and its nature appeared to determine the degree of the response.
Collapse
Affiliation(s)
- Anna M A De Rentiis
- Institute and Outpatient Clinic of Occupational, Social and Environmental Medicine, Friedrich-Alexander-University Erlangen-Nürnberg (FAU), Erlangen, Germany
| | - Mario Pink
- Institute and Outpatient Clinic of Occupational, Social and Environmental Medicine, Friedrich-Alexander-University Erlangen-Nürnberg (FAU), Erlangen, Germany.,Department of Chemical and Product Safety, German Federal Institute for Risk Assessment (BfR), Berlin, Germany
| | - Nisha Verma
- Institute and Outpatient Clinic of Occupational, Social and Environmental Medicine, Friedrich-Alexander-University Erlangen-Nürnberg (FAU), Erlangen, Germany
| | - Simone Schmitz-Spanke
- Institute and Outpatient Clinic of Occupational, Social and Environmental Medicine, Friedrich-Alexander-University Erlangen-Nürnberg (FAU), Erlangen, Germany
| |
Collapse
|
|
26
|
Pavan C, Santalucia R, Leinardi R, Fabbiani M, Yakoub Y, Uwambayinema F, Ugliengo P, Tomatis M, Martra G, Turci F, Lison D, Fubini B. Nearly free surface silanols are the critical molecular moieties that initiate the toxicity of silica particles. Proc Natl Acad Sci U S A 2020; 117:27836-27846. [PMID: 33097669 PMCID: PMC7668052 DOI: 10.1073/pnas.2008006117] [Citation(s) in RCA: 64] [Impact Index Per Article: 12.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/14/2022] Open
Abstract
Inhalation of silica particles can induce inflammatory lung reactions that lead to silicosis and/or lung cancer when the particles are biopersistent. This toxic activity of silica dusts is extremely variable depending on their source and preparation methods. The exact molecular moiety that explains and predicts this variable toxicity of silica remains elusive. Here, we have identified a unique subfamily of silanols as the major determinant of silica particle toxicity. This population of "nearly free silanols" (NFS) appears on the surface of quartz particles upon fracture and can be modulated by thermal treatments. Density functional theory calculations indicates that NFS locate at an intersilanol distance of 4.00 to 6.00 Å and form weak mutual interactions. Thus, NFS could act as an energetically favorable moiety at the surface of silica for establishing interactions with cell membrane components to initiate toxicity. With ad hoc prepared model quartz particles enriched or depleted in NFS, we demonstrate that NFS drive toxicity, including membranolysis, in vitro proinflammatory activity, and lung inflammation. The toxic activity of NFS is confirmed with pyrogenic and vitreous amorphous silica particles, and industrial quartz samples with noncontrolled surfaces. Our results identify the missing key molecular moieties of the silica surface that initiate interactions with cell membranes, leading to pathological outcomes. NFS may explain other important interfacial processes involving silica particles.
Collapse
Affiliation(s)
- Cristina Pavan
- Louvain Centre for Toxicology and Applied Pharmacology, UCLouvain, 1200 Brussels, Belgium
- Department of Chemistry, University of Turin, 10124 Turin, Italy
- "G. Scansetti" Interdepartmental Centre for Studies on Asbestos and Other Toxic Particulates, 10125 Turin, Italy
| | - Rosangela Santalucia
- Department of Chemistry, University of Turin, 10124 Turin, Italy
- Nanostructured Interfaces and Surfaces Interdepartmental Centre, 10125 Turin, Italy
| | - Riccardo Leinardi
- Louvain Centre for Toxicology and Applied Pharmacology, UCLouvain, 1200 Brussels, Belgium
- Department of Chemistry, University of Turin, 10124 Turin, Italy
- "G. Scansetti" Interdepartmental Centre for Studies on Asbestos and Other Toxic Particulates, 10125 Turin, Italy
| | - Marco Fabbiani
- Department of Chemistry, University of Turin, 10124 Turin, Italy
- Nanostructured Interfaces and Surfaces Interdepartmental Centre, 10125 Turin, Italy
| | - Yousof Yakoub
- Louvain Centre for Toxicology and Applied Pharmacology, UCLouvain, 1200 Brussels, Belgium
| | - Francine Uwambayinema
- Louvain Centre for Toxicology and Applied Pharmacology, UCLouvain, 1200 Brussels, Belgium
| | - Piero Ugliengo
- Department of Chemistry, University of Turin, 10124 Turin, Italy
- Nanostructured Interfaces and Surfaces Interdepartmental Centre, 10125 Turin, Italy
| | - Maura Tomatis
- Department of Chemistry, University of Turin, 10124 Turin, Italy
- "G. Scansetti" Interdepartmental Centre for Studies on Asbestos and Other Toxic Particulates, 10125 Turin, Italy
- Nanostructured Interfaces and Surfaces Interdepartmental Centre, 10125 Turin, Italy
| | - Gianmario Martra
- Department of Chemistry, University of Turin, 10124 Turin, Italy
- "G. Scansetti" Interdepartmental Centre for Studies on Asbestos and Other Toxic Particulates, 10125 Turin, Italy
- Nanostructured Interfaces and Surfaces Interdepartmental Centre, 10125 Turin, Italy
| | - Francesco Turci
- Department of Chemistry, University of Turin, 10124 Turin, Italy;
- "G. Scansetti" Interdepartmental Centre for Studies on Asbestos and Other Toxic Particulates, 10125 Turin, Italy
- Nanostructured Interfaces and Surfaces Interdepartmental Centre, 10125 Turin, Italy
| | - Dominique Lison
- Louvain Centre for Toxicology and Applied Pharmacology, UCLouvain, 1200 Brussels, Belgium;
| | - Bice Fubini
- Department of Chemistry, University of Turin, 10124 Turin, Italy
- "G. Scansetti" Interdepartmental Centre for Studies on Asbestos and Other Toxic Particulates, 10125 Turin, Italy
| |
Collapse
|
|
27
|
Evaluation of the NLRP3 Inflammasome Activating Effects of a Large Panel of TiO 2 Nanomaterials in Macrophages. NANOMATERIALS 2020; 10:nano10091876. [PMID: 32961672 PMCID: PMC7558067 DOI: 10.3390/nano10091876] [Citation(s) in RCA: 16] [Impact Index Per Article: 3.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 07/16/2020] [Revised: 09/10/2020] [Accepted: 09/15/2020] [Indexed: 12/12/2022]
Abstract
TiO2 nanomaterials are among the most commonly produced and used engineered nanomaterials (NMs) in the world. There is controversy regarding their ability to induce inflammation-mediated lung injuries following inhalation exposure. Activation of the NACHT, LRR and PYD domains-containing protein 3 (NALP3) inflammasome and subsequent release of the cytokine interleukin (IL)-1β in pulmonary macrophages has been postulated as an essential pathway for the inflammatory and associated tissue-remodeling effects of toxic particles. Our study aim was to determine and rank the IL-1β activating properties of TiO2 NMs by comparing a large panel of different samples against each other as well as against fine TiO2, synthetic amorphous silica and crystalline silica (DQ12 quartz). Effects were evaluated in primary bone marrow derived macrophages (BMDMs) from NALP3-deficient and proficient mice as well as in the rat alveolar macrophage cell line NR8383. Our results show that specific TiO2 NMs can activate the inflammasome in macrophages albeit with a markedly lower potency than amorphous SiO2 and quartz. The heterogeneity in IL-1β release observed in our study among 19 different TiO2 NMs underscores the relevance of case-by-case evaluation of nanomaterials of similar chemical composition. Our findings also further promote the NR8383 cell line as a promising in vitro tool for the assessment of the inflammatory and inflammasome activating properties of NMs.
Collapse
|
|
28
|
Chen YW, Huang MZ, Chen CL, Kuo CY, Yang CY, Chiang-Ni C, Chen YYM, Hsieh CM, Wu HY, Kuo ML, Chiu CH, Lai CH. PM 2.5 impairs macrophage functions to exacerbate pneumococcus-induced pulmonary pathogenesis. Part Fibre Toxicol 2020; 17:37. [PMID: 32753046 PMCID: PMC7409448 DOI: 10.1186/s12989-020-00362-2] [Citation(s) in RCA: 36] [Impact Index Per Article: 7.2] [Reference Citation Analysis] [Abstract] [Key Words] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/30/2019] [Accepted: 07/03/2020] [Indexed: 02/06/2023] Open
Abstract
Background Pneumococcus is one of the most common human airway pathogens that causes life-threatening infections. Ambient fine particulate matter (PM) with aerodynamic diameter ≤ 2.5 μm (PM2.5) is known to significantly contribute to respiratory diseases. PM2.5-induced airway inflammation may decrease innate immune defenses against bacterial infection. However, there is currently limited information available regarding the effect of PM2.5 exposure on molecular interactions between pneumococcus and macrophages. Results PM2.5 exposure hampered macrophage functions, including phagocytosis and proinflammatory cytokine production, in response to pneumococcal infection. In a PM2.5-exposed pneumococcus-infected mouse model, PM2.5 subverted the pulmonary immune response and caused leukocyte infiltration. Further, PM2.5 exposure suppressed the levels of CXCL10 and its receptor, CXCR3, by inhibiting the PI3K/Akt and MAPK pathways. Conclusions The effect of PM2.5 exposure on macrophage activity enhances pneumococcal infectivity and aggravates pulmonary pathogenesis.
Collapse
Affiliation(s)
- Yu-Wen Chen
- Graduate Institute of Biomedical Sciences, Department of Microbiology and Immunology, College of Medicine, Chang Gung University, Taoyuan, Taiwan
| | - Mei-Zi Huang
- Graduate Institute of Biomedical Sciences, Department of Microbiology and Immunology, College of Medicine, Chang Gung University, Taoyuan, Taiwan
| | - Chyi-Liang Chen
- Department of Pediatrics, Molecular Infectious Disease Research Center, Chang Gung Memorial Hospital, Linkou, Taiwan
| | - Chieh-Ying Kuo
- Graduate Institute of Biomedical Sciences, Department of Microbiology and Immunology, College of Medicine, Chang Gung University, Taoyuan, Taiwan
| | - Chia-Yu Yang
- Graduate Institute of Biomedical Sciences, Department of Microbiology and Immunology, College of Medicine, Chang Gung University, Taoyuan, Taiwan.,Molecular Medicine Research Center, Chang Gung University, Taoyuan, Taiwan.,Department of Otolaryngology-Head and Neck Surgery, Chang Gung Memorial Hospital, Taoyuan, Taiwan
| | - Chuan Chiang-Ni
- Graduate Institute of Biomedical Sciences, Department of Microbiology and Immunology, College of Medicine, Chang Gung University, Taoyuan, Taiwan.,Department of Pediatrics, Molecular Infectious Disease Research Center, Chang Gung Memorial Hospital, Linkou, Taiwan
| | - Yi-Ywan M Chen
- Graduate Institute of Biomedical Sciences, Department of Microbiology and Immunology, College of Medicine, Chang Gung University, Taoyuan, Taiwan.,Department of Pediatrics, Molecular Infectious Disease Research Center, Chang Gung Memorial Hospital, Linkou, Taiwan
| | - Chia-Ming Hsieh
- Graduate Institute of Biomedical Sciences, Department of Microbiology and Immunology, College of Medicine, Chang Gung University, Taoyuan, Taiwan
| | - Hui-Yu Wu
- Graduate Institute of Biomedical Sciences, Department of Microbiology and Immunology, College of Medicine, Chang Gung University, Taoyuan, Taiwan
| | - Ming-Ling Kuo
- Graduate Institute of Biomedical Sciences, Department of Microbiology and Immunology, College of Medicine, Chang Gung University, Taoyuan, Taiwan.,Division of Allergy, Asthma, and Rheumatology, Department of Pediatrics, Chang Gung Memorial Hospital, Linkou, Taiwan
| | - Cheng-Hsun Chiu
- Graduate Institute of Biomedical Sciences, Department of Microbiology and Immunology, College of Medicine, Chang Gung University, Taoyuan, Taiwan.,Department of Pediatrics, Molecular Infectious Disease Research Center, Chang Gung Memorial Hospital, Linkou, Taiwan
| | - Chih-Ho Lai
- Graduate Institute of Biomedical Sciences, Department of Microbiology and Immunology, College of Medicine, Chang Gung University, Taoyuan, Taiwan. .,Department of Pediatrics, Molecular Infectious Disease Research Center, Chang Gung Memorial Hospital, Linkou, Taiwan. .,Department of Microbiology, School of Medicine, China Medical University, Taichung, Taiwan. .,Department of Nursing, Asia University, Taichung, Taiwan.
| |
Collapse
|
|
29
|
Carbon Nanotubes under Scrutiny: Their Toxicity and Utility in Mesothelioma Research. APPLIED SCIENCES-BASEL 2020. [DOI: 10.3390/app10134513] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 01/18/2023]
Abstract
Research on the toxicity of engineered carbon nanotubes (CNT) was initiated by Belgian academic chemists and toxicologists more than 15 years ago. It is now undisputed that some of these attractive nanomaterials induce serious illness such as fibrosis and cancer. The physico-chemical determinants of CNT-induced adverse effects are now elucidated and include shape, nanoscale diameter, and structural defects. Generated in vitro and in vivo data on their inflammogenic and fibrogenic activities were combined and translated in AOP (adverse outcome pathways) available for risk assessment and regulatory policies. The asbestos-like carcinogenic effect of CNT, notably their capacity to induce malignant mesothelioma (MM), remain, however, a cause of concern for public health and strongly curb the craze for CNT in industries. MM still represents a real challenge for clinicians and a highly refractory cancer to existing therapeutic strategies. By comparing mesotheliomagenic CNT (needle-like CNT-N) to non mesotheliomagenic CNT (tangled-like CNT-T), our group generated a relevant animal model that highlights immune pathways specifically associated to the carcinogenic process. Evidence indicates that only CNT-N possess the intrinsic capacity to induce a preferential, rapid, and sustained accumulation of host immunosuppressive cells that subvert immune surveillance and suppress anti-mesothelioma immunity. This new concept offers novel horizons for the clinical management of mesothelioma and represents an additional tool for predicting the mesotheliomagenic activity of newly elaborated CNT or nanoparticles.
Collapse
|
|
30
|
Leinardi R, Pavan C, Yedavally H, Tomatis M, Salvati A, Turci F. Cytotoxicity of fractured quartz on THP-1 human macrophages: role of the membranolytic activity of quartz and phagolysosome destabilization. Arch Toxicol 2020; 94:2981-2995. [PMID: 32592078 PMCID: PMC7415752 DOI: 10.1007/s00204-020-02819-x] [Citation(s) in RCA: 14] [Impact Index Per Article: 2.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/07/2020] [Accepted: 06/18/2020] [Indexed: 12/13/2022]
Abstract
The pathogenicity of quartz involves lysosomal alteration in alveolar macrophages. This event triggers the inflammatory cascade that may lead to quartz-induced silicosis and eventually lung cancer. Experiments with synthetic quartz crystals recently showed that quartz dust is cytotoxic only when the atomic order of the crystal surfaces is upset by fracturing. Cytotoxicity was not observed when quartz had as-grown, unfractured surfaces. These findings raised questions on the potential impact of quartz surfaces on the phagolysosomal membrane upon internalization of the particles by macrophages. To gain insights on the surface-induced cytotoxicity of quartz, as-grown and fractured quartz particles in respirable size differing only in surface properties related to fracturing were prepared and physico-chemically characterized. Synthetic quartz particles were compared to a well-known toxic commercial quartz dust. Membranolysis was assessed on red blood cells, and quartz uptake, cell viability and effects on lysosomes were assessed on human PMA-differentiated THP-1 macrophages, upon exposing cells to increasing concentrations of quartz particles (10–250 µg/ml). All quartz samples were internalized, but only fractured quartz elicited cytotoxicity and phagolysosomal alterations. These effects were blunted when uptake was suppressed by incubating macrophages with particles at 4 °C. Membranolysis, but not cytotoxicity, was quenched when fractured quartz was incubated with cells in protein-supplemented medium. We propose that, upon internalization, the phagolysosome environment rapidly removes serum proteins from the quartz surface, restoring quartz membranolytic activity in the phagolysosomes. Our findings indicate that the cytotoxic activity of fractured quartz is elicited by promoting phagolysosomal membrane alteration.
Collapse
Affiliation(s)
- Riccardo Leinardi
- "G. Scansetti" Interdepartmental Center for Studies On Asbestos and Other Toxic Particulates, Department of Chemistry, University of Torino, Via P. Giuria 7, 10125, Turin, Italy
| | - Cristina Pavan
- Louvain Centre for Toxicology and Applied Pharmacology (LTAP), Université Catholique de Louvain, Avenue Hippocrate 57, 1200, Brussels, Belgium
| | - Harita Yedavally
- Department of Nanomedicine & Drug Targeting, Groningen Research Institute of Pharmacy (GRIP), University of Groningen, Antonius Deusinglaan 1, Groningen, 9713 AV, The Netherlands
| | - Maura Tomatis
- "G. Scansetti" Interdepartmental Center for Studies On Asbestos and Other Toxic Particulates, Department of Chemistry, University of Torino, Via P. Giuria 7, 10125, Turin, Italy
| | - Anna Salvati
- Department of Nanomedicine & Drug Targeting, Groningen Research Institute of Pharmacy (GRIP), University of Groningen, Antonius Deusinglaan 1, Groningen, 9713 AV, The Netherlands.
| | - Francesco Turci
- "G. Scansetti" Interdepartmental Center for Studies On Asbestos and Other Toxic Particulates, Department of Chemistry, University of Torino, Via P. Giuria 7, 10125, Turin, Italy.
| |
Collapse
|
|
31
|
Colaço M, Duarte A, Zuzarte M, Costa BFO, Borges O. Airborne environmental fine particles induce intense inflammatory response regardless of the absence of heavy metal elements. ECOTOXICOLOGY AND ENVIRONMENTAL SAFETY 2020; 195:110500. [PMID: 32222596 DOI: 10.1016/j.ecoenv.2020.110500] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 12/13/2019] [Revised: 03/11/2020] [Accepted: 03/16/2020] [Indexed: 06/10/2023]
Abstract
Airborne environmental particles (EP) more commonly referred as particulate matter (PM) are an illustrative marker of air pollution that is associated with adverse effects on human health. Considering, PM is a complex mixture, not only in terms of its chemical composition, but also in the range of particle size, it is difficult to identify which attribute contributes more for the toxicity. Currently, there is no report about the immunotoxicological effects caused by PM with reduced content of heavy metals. This study intends to address this gap and provides a detailed characterization and immunotoxicity evaluation of PM collected in an urban area with heavy traffic congestion. Environmental particles were separated by different sizes though a sucrose gradient. This method allowed to achieve 4 sized fractions: EP f 15 % with a mean diameter of 284 nm ± 1.86 nm, EP f 25 % with a mean diameter of 461 nm ± 1.72 nm, EP f 35 % with a mean diameter of 1845 nm ± 251 nm and EP f 45 % with a mean diameter of 2204 nm ± 310 nm. Only the fractions with the smallest sizes (EP f 15 % and EP f 25 %) were subsequently studied. The chemical composition of both fractions was not substantially different, and the dominant elements were C, O, Ca and K. Only EP f 25 % showed to have a small amount of Fe. Therefore, the heavy metal elements were eliminated through centrifugation. Essentially, we found that the EP f 15 % was more cytotoxic in RAW 264.7 cells than EP f 25 %, which indicates the smaller size as the motive for the higher toxicity. In addition, both fractions of EP presented a good internalization in macrophages after 2 h exposure and induced the production of reactive oxygen species in a concentration-dependent manner. Moreover, EP f 15 % and EP f 25 % led to a strong secretion of proinflammatory cytokines (TNF-α and IL-6) in human peripheral blood mononuclear cells (hPBMCs) in the 3 concentrations tested. The inflammatory response observed was independent of the presence of heavy metals and endotoxins, since these last were suppressed by using polymyxin B sulfate. This report emphasizes the importance of an adequate physicochemical characterization and adequate controls in the experiments to achieve a right interpretation of the biological effects caused by PM.
Collapse
Affiliation(s)
- Mariana Colaço
- Center for Neuroscience and Cell Biology, University of Coimbra, Coimbra, Portugal; Faculty of Pharmacy, University of Coimbra, Coimbra, Portugal
| | - Alana Duarte
- Center for Neuroscience and Cell Biology, University of Coimbra, Coimbra, Portugal; Faculty of Pharmacy, University of Coimbra, Coimbra, Portugal
| | - Mónica Zuzarte
- Coimbra Institute for Clinical and Biomedical Research (iCBR), Faculty of Medicine, University of Coimbra, Coimbra, Portugal
| | - Benilde F O Costa
- CFisUC, Physics Department, University of Coimbra, 3004-516, Coimbra, Portugal
| | - Olga Borges
- Center for Neuroscience and Cell Biology, University of Coimbra, Coimbra, Portugal; Faculty of Pharmacy, University of Coimbra, Coimbra, Portugal.
| |
Collapse
|
|
32
|
Skuland T, Låg M, Gutleb AC, Brinchmann BC, Serchi T, Øvrevik J, Holme JA, Refsnes M. Pro-inflammatory effects of crystalline- and nano-sized non-crystalline silica particles in a 3D alveolar model. Part Fibre Toxicol 2020; 17:13. [PMID: 32316988 PMCID: PMC7175518 DOI: 10.1186/s12989-020-00345-3] [Citation(s) in RCA: 42] [Impact Index Per Article: 8.4] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/19/2019] [Accepted: 04/07/2020] [Indexed: 12/27/2022] Open
Abstract
BACKGROUND Silica nanoparticles (SiNPs) are among the most widely manufactured and used nanoparticles. Concerns about potential health effects of SiNPs have therefore risen. Using a 3D tri-culture model of the alveolar lung barrier we examined effects of exposure to SiNPs (Si10) and crystalline silica (quartz; Min-U-Sil) in the apical compartment consisting of human alveolar epithelial A549 cells and THP-1-derived macrophages, as well as in the basolateral compartment with Ea.hy926 endothelial cells. Inflammation-related responses were measured by ELISA and gene expression. RESULTS Exposure to both Si10 and Min-U-Sil induced gene expression and release of CXCL8, interleukin-6 (IL-6), tumor necrosis factor-α (TNF-α), interleukin-1α (IL-1α) and interleukin-1β (IL-1β) in a concentration-dependent manner. Cytokine/chemokine expression and protein levels were highest in the apical compartment. Si10 and Min-U-Sil also induced expression of adhesion molecules ICAM-1 and E-selectin in the apical compartment. In the basolateral endothelial compartment we observed marked, but postponed effects on expression of all these genes, but only at the highest particle concentrations. Geneexpressions of heme oxygenase-1 (HO-1) and the metalloproteases (MMP-1 and MMP-9) were less affected. The IL-1 receptor antagonist (IL-1RA), markedly reduced effects of Si10 and Min-U-Sil exposures on gene expression of cytokines and adhesion molecules, as well as cytokine-release in both compartments. CONCLUSIONS Si10 and Min-U-Sil induced gene expression and release of pro-inflammatory cytokines/adhesion molecules at both the epithelial/macrophage and endothelial side of a 3D tri-culture. Responses in the basolateral endothelial cells were only induced at high concentrations, and seemed to be mediated by IL-1α/β released from the apical epithelial cells and macrophages.
Collapse
Affiliation(s)
- Tonje Skuland
- Section of Air Pollution and Noise, Department of Environment and Health, Norwegian Institute of Public Health, PO Box 4404 Nydalen, N-0403, Oslo, Norway.
| | - Marit Låg
- Section of Air Pollution and Noise, Department of Environment and Health, Norwegian Institute of Public Health, PO Box 4404 Nydalen, N-0403, Oslo, Norway
| | - Arno C Gutleb
- Environmental Research and Innovation (ERIN), Luxembourg Institute of Science and Technology (LIST), Belvaux, Grand Duchy of Luxembourg, Luxembourg
| | - Bendik C Brinchmann
- Section of Air Pollution and Noise, Department of Environment and Health, Norwegian Institute of Public Health, PO Box 4404 Nydalen, N-0403, Oslo, Norway
- Department of Occupational Medicine and Epidemiology, National Institute of Occupational Health, Oslo, Norway
| | - Tommaso Serchi
- Environmental Research and Innovation (ERIN), Luxembourg Institute of Science and Technology (LIST), Belvaux, Grand Duchy of Luxembourg, Luxembourg
| | - Johan Øvrevik
- Section of Air Pollution and Noise, Department of Environment and Health, Norwegian Institute of Public Health, PO Box 4404 Nydalen, N-0403, Oslo, Norway
- Department of Biosciences, Faculty of Mathematics and Natural Sciences, University of Oslo, Oslo, Norway
| | - Jørn A Holme
- Section of Air Pollution and Noise, Department of Environment and Health, Norwegian Institute of Public Health, PO Box 4404 Nydalen, N-0403, Oslo, Norway
| | - Magne Refsnes
- Section of Air Pollution and Noise, Department of Environment and Health, Norwegian Institute of Public Health, PO Box 4404 Nydalen, N-0403, Oslo, Norway
| |
Collapse
|
|
33
|
Silica dioxide nanoparticles aggravate airway inflammation in an asthmatic mouse model via NLRP3 inflammasome activation. Regul Toxicol Pharmacol 2020; 112:104618. [PMID: 32087352 DOI: 10.1016/j.yrtph.2020.104618] [Citation(s) in RCA: 29] [Impact Index Per Article: 5.8] [Reference Citation Analysis] [Abstract] [Key Words] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/23/2019] [Revised: 01/22/2020] [Accepted: 02/18/2020] [Indexed: 12/18/2022]
Abstract
Silica dioxide nanoparticles (SiONPs) are mainly used in the rubber industry; however, they are a major air pollutant in Asia. Thus, extensive research on this issue is required. In this study, we investigated the effects of SiONPs on asthma aggravation and elucidated the underlying mechanism using ovalbumin (OVA)-induced asthmatic mice model and in NCI-H292 cells. Mice exposed to SiONPs showed markedly increased Penh values, inflammatory cell counts, and inflammatory cytokine levels compared to OVA-induced asthmatic mice. Exposure to SiONPs also induced additional airway inflammation and mucus secretion with increases in protein expression levels of thioredoxin-interacting protein (TXNIP), NOD-like receptor pyrin domain-containing 3 (NLRP3) inflammasome, and interleukin (IL)-1β compared to those in OVA-induced asthmatic mice. Treatment of SiONPs in NCI-H292 cells also significantly increased mRNA expression levels of inflammatory cytokines accompanied with elevation in the levels of TXNIP, NLRP3 inflammasome, and IL-1β proteins in a concentration-dependent manner. Taken together, exposure to SiONPs aggravated asthma development, which is closely related to inflammasome activation. Our results provide useful information about the toxicological effects of SiONPs on asthma exacerbation and suggest the need to avoid SiONP exposure especially in individuals with respiratory diseases.
Collapse
|
|
34
|
Gao R, Sang N. Quasi-ultrafine particles promote cell metastasis via HMGB1-mediated cancer cell adhesion. ENVIRONMENTAL POLLUTION (BARKING, ESSEX : 1987) 2020; 256:113390. [PMID: 31706768 DOI: 10.1016/j.envpol.2019.113390] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 04/09/2019] [Revised: 10/11/2019] [Accepted: 10/12/2019] [Indexed: 06/10/2023]
Abstract
With increasingly severe air pollution, the aggravated health risks of particulate matter, especially ultrafine particles, are emerging as an urgent and sensitive topic. Considering the heterogeneity and complexity of ultrafine particles, there is insufficient evidence about their toxic effects and possible molecular mechanisms. To address this question, we analyzed the emission characteristics of quasi-ultrafine particles collected during winter in a typical coal-burning city, Taiyuan, and confirmed their contribution to lung cancer cell adhesion and metastasis. For the specific mechanism, we revealed that the endocytosis of quasi-ultrafine particles stimulated the release of HMGB1, induced NFκB-facilitated proinflammatory cytokine production through the interaction of HMGB1 with RAGE, and resulted in cancer-endothelial cell adhesion. These findings remind us of the potential effects of anthropogenic quasi-ultrafine particle pollution and provide a theoretical reference for the mitigation of tumorigenesis in a severe particulate matter contaminated environment.
Collapse
Affiliation(s)
- Rui Gao
- College of Environment and Resource, Research Center of Environment and Health, Shanxi University, Taiyuan, Shanxi, 030006, People's Republic of China
| | - Nan Sang
- College of Environment and Resource, Research Center of Environment and Health, Shanxi University, Taiyuan, Shanxi, 030006, People's Republic of China.
| |
Collapse
|
|
35
|
Benninghoff AD, Bates MA, Chauhan PS, Wierenga KA, Gilley KN, Holian A, Harkema JR, Pestka JJ. Docosahexaenoic Acid Consumption Impedes Early Interferon- and Chemokine-Related Gene Expression While Suppressing Silica-Triggered Flaring of Murine Lupus. Front Immunol 2019; 10:2851. [PMID: 31921124 PMCID: PMC6923248 DOI: 10.3389/fimmu.2019.02851] [Citation(s) in RCA: 21] [Impact Index Per Article: 3.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/02/2019] [Accepted: 11/20/2019] [Indexed: 12/18/2022] Open
Abstract
Exposure of lupus-prone female NZBWF1 mice to respirable crystalline silica (cSiO2), a known human autoimmune trigger, initiates loss of tolerance, rapid progression of autoimmunity, and early onset of glomerulonephritis. We have previously demonstrated that dietary supplementation with the ω-3 polyunsaturated fatty acid docosahexaenoic acid (DHA) suppresses autoimmune pathogenesis and nephritis in this unique model of lupus flaring. In this report, we utilized tissues from prior studies to test the hypothesis that DHA consumption interferes with upregulation of critical genes associated with cSiO2-triggered murine lupus. A NanoString nCounter platform targeting 770 immune-related genes was used to assess the effects cSiO2 on mRNA signatures over time in female NZBWF1 mice consuming control (CON) diets compared to mice fed diets containing DHA at an amount calorically equivalent to human consumption of 2 g per day (DHA low) or 5 g per day (DHA high). Experimental groups of mice were sacrificed: (1) 1 d after a single intranasal instillation of 1 mg cSiO2 or vehicle, (2) 1 d after four weekly single instillations of vehicle or 1 mg cSiO2, and (3) 1, 5, 9, and 13 weeks after four weekly single instillations of vehicle or 1 mg cSiO2. Genes associated with inflammation as well as innate and adaptive immunity were markedly upregulated in lungs of CON-fed mice 1 d after four weekly cSiO2 doses but were significantly suppressed in mice fed DHA high diets. Importantly, mRNA signatures in lungs of cSiO2-treated CON-fed mice over 13 weeks reflected progressive amplification of interferon (IFN)- and chemokine-related gene pathways. While these responses in the DHA low group were suppressed primarily at week 5, significant downregulation was observed at weeks 1, 5, 9, and 13 in mice fed the DHA high diet. At week 13, cSiO2 treatment of CON-fed mice affected 214 genes in kidney tissue associated with inflammation, innate/adaptive immunity, IFN, chemokines, and antigen processing, mostly by upregulation; however, feeding DHA dose-dependently suppressed these responses. Taken together, dietary DHA intake in lupus-prone mice impeded cSiO2-triggered mRNA signatures known to be involved in ectopic lymphoid tissue neogenesis, systemic autoimmunity, and glomerulonephritis.
Collapse
Affiliation(s)
- Abby D. Benninghoff
- Department of Animal, Dairy and Veterinary Sciences and The School of Veterinary Medicine, Utah State University, Logan, UT, United States
| | - Melissa A. Bates
- Department of Food Science and Human Nutrition, Michigan State University, East Lansing, MI, United States
- Institute for Integrative Toxicology, Michigan State University, East Lansing, MI, United States
| | - Preeti S. Chauhan
- Department of Food Science and Human Nutrition, Michigan State University, East Lansing, MI, United States
| | - Kathryn A. Wierenga
- Institute for Integrative Toxicology, Michigan State University, East Lansing, MI, United States
- Department of Biochemistry and Molecular Biology, Michigan State University, East Lansing, MI, United States
| | - Kristen N. Gilley
- Department of Food Science and Human Nutrition, Michigan State University, East Lansing, MI, United States
| | - Andrij Holian
- Department of Biomedical and Pharmaceutical Sciences, Center for Environmental Health Sciences, University of Montana, Missoula, MT, United States
| | - Jack R. Harkema
- Institute for Integrative Toxicology, Michigan State University, East Lansing, MI, United States
- Department of Pathobiology and Diagnostic Investigation, Michigan State University, East Lansing, MI, United States
| | - James J. Pestka
- Department of Food Science and Human Nutrition, Michigan State University, East Lansing, MI, United States
- Institute for Integrative Toxicology, Michigan State University, East Lansing, MI, United States
- Department of Microbiology and Molecular Genetics, Michigan State University, East Lansing, MI, United States
| |
Collapse
|
|
36
|
Brilland B, Beauvillain C, Mazurkiewicz G, Rucay P, Roquelaure Y, Tabiasco J, Vinatier E, Riou J, Jeannin P, Renier G, Subra JF, Augusto JF. T Cell Dysregulation in Non-silicotic Silica Exposed Workers: A Step Toward Immune Tolerance Breakdown. Front Immunol 2019; 10:2743. [PMID: 31824514 PMCID: PMC6883424 DOI: 10.3389/fimmu.2019.02743] [Citation(s) in RCA: 15] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/23/2019] [Accepted: 11/08/2019] [Indexed: 12/26/2022] Open
Abstract
Background: Chronic silica exposure can lead to silicosis, complicated or not by autoimmune diseases (AID). The pathophysiology of silica-induced AID remains not fully understood, especially immune mechanisms that may develop in patients without yet established silicosis. We conducted a prospective clinical study to analyze the impact of crystalline silica (CS) on T cell phenotype and regulatory T cells (Tregs) frequency, as well as on auto-antibodies development in non-silicotic workers exposed to CS. Methods: Workers with moderate to high exposure level to CS and aged between 30 and 60 years-old were considered for inclusion. Peripheral blood mononuclear cells were analyzed by flow cytometry. Auto-antibodies were screened in serum by immunofluorescence. Blood from 42 and 45 healthy subjects (HC) was used as control for T cell phenotype and serum analyses, respectively. Results: Among the 63 included workers exposed to CS, 55 had full data available and were analyzed. Ten were exposed to CS for <5 years, 18 for 5–10 years and 27 for more than 10 years. The frequency of Tregs (CD4+CD25+CD127−FoxP3+) was significantly lower in CS exposed workers as compared to HC. We found an increased expression of the activation marker HLA-DR on T cells (CD3+, CD4+, and CD8+) of CS exposed workers as compared to HC. Tregs to activated T cells ratio was also lower in exposed subjects. In the latter, HLA-DR expression level and Tregs frequency were significantly associated with CS exposure duration. Serum autoantibody detection was significantly higher in CS exposed workers as compared to HC. Especially, among workers exposed more than 10 years, antinuclear antibodies and ANCA were detected in 44 and 22% among them, as compared to 5 and 2.5% in HC, respectively. Conclusion: This work shows that CS exposure is associated with a decrease of Tregs frequency, an increase of T cell activation status, and a tolerance breakdown against auto-antigens. These results show that alterations of the T cell compartment can be detected early over the course of CS exposure, preceding silicosis development or AID onset.
Collapse
Affiliation(s)
- Benoit Brilland
- Service de Néphrologie-Dialyse-Transplantation, CHU d'Angers, Angers, France.,CRCINA, INSERM, Université de Nantes, Université d'Angers, Angers, France
| | - Céline Beauvillain
- CRCINA, INSERM, Université de Nantes, Université d'Angers, Angers, France.,Laboratoire d'Immunologie et d'Allergologie, CHU d'Angers, Angers, France
| | - Gery Mazurkiewicz
- Service Santé au Travail Côte de Lumière, Les Sables-d'Olonne, France
| | - Pierre Rucay
- Service de Médecine du Travail, CHU d'Angers, Angers, France
| | - Yves Roquelaure
- Service de Médecine du Travail, CHU d'Angers, Angers, France
| | - Julie Tabiasco
- CRCINA, INSERM, Université de Nantes, Université d'Angers, Angers, France
| | - Emeline Vinatier
- CRCINA, INSERM, Université de Nantes, Université d'Angers, Angers, France.,Laboratoire d'Immunologie et d'Allergologie, CHU d'Angers, Angers, France
| | - Jérémie Riou
- MINT, UNIV Angers, INSERM 1066, CNRS 6021, IBS- CHU, Angers, France
| | - Pascale Jeannin
- CRCINA, INSERM, Université de Nantes, Université d'Angers, Angers, France.,Laboratoire d'Immunologie et d'Allergologie, CHU d'Angers, Angers, France
| | - Gilles Renier
- Laboratoire d'Immunologie et d'Allergologie, CHU d'Angers, Angers, France
| | - Jean-François Subra
- Service de Néphrologie-Dialyse-Transplantation, CHU d'Angers, Angers, France.,CRCINA, INSERM, Université de Nantes, Université d'Angers, Angers, France
| | - Jean-François Augusto
- Service de Néphrologie-Dialyse-Transplantation, CHU d'Angers, Angers, France.,CRCINA, INSERM, Université de Nantes, Université d'Angers, Angers, France
| |
Collapse
|
|
37
|
Toll-Like Receptors 2 and 4 Modulate Pulmonary Inflammation and Host Factors Mediated by Outer Membrane Vesicles Derived from Acinetobacter baumannii. Infect Immun 2019; 87:IAI.00243-19. [PMID: 31262980 DOI: 10.1128/iai.00243-19] [Citation(s) in RCA: 33] [Impact Index Per Article: 5.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/03/2019] [Accepted: 06/11/2019] [Indexed: 11/20/2022] Open
Abstract
Pneumonia due to Gram-negative bacteria is associated with high mortality. Acinetobacter baumannii is a Gram-negative bacterium that is associated with hospital-acquired and ventilator-associated pneumonia. Bacteria have been described to release outer membrane vesicles (OMVs) that are capable of mediating systemic inflammation. The mechanism by which A. baumannii OMVs mediate inflammation is not fully defined. We sought to investigate the roles that Toll-like receptors (TLRs) play in A. baumannii OMV-mediated pulmonary inflammation. We isolated OMVs from A. baumannii cultures and intranasally introduced the OMVs into mice. Intranasal introduction of A. baumannii OMVs mediated pulmonary inflammation, which is associated with neutrophil recruitment and weight loss. In addition, A. baumannii OMVs increased the release of several chemokines and cytokines in the mouse lungs. The proinflammatory responses were partially inhibited in TLR2- and TLR4-deficient mice compared to those of wild-type mice. This study highlights the important roles of TLRs in A. baumannii OMV-induced pulmonary inflammation in vivo.
Collapse
|
|
38
|
Pavan C, Delle Piane M, Gullo M, Filippi F, Fubini B, Hoet P, Horwell CJ, Huaux F, Lison D, Lo Giudice C, Martra G, Montfort E, Schins R, Sulpizi M, Wegner K, Wyart-Remy M, Ziemann C, Turci F. The puzzling issue of silica toxicity: are silanols bridging the gaps between surface states and pathogenicity? Part Fibre Toxicol 2019; 16:32. [PMID: 31419990 PMCID: PMC6697921 DOI: 10.1186/s12989-019-0315-3] [Citation(s) in RCA: 63] [Impact Index Per Article: 10.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/21/2019] [Accepted: 08/05/2019] [Indexed: 12/20/2022] Open
Abstract
BACKGROUND Silica continues to represent an intriguing topic of fundamental and applied research across various scientific fields, from geology to physics, chemistry, cell biology, and particle toxicology. The pathogenic activity of silica is variable, depending on the physico-chemical features of the particles. In the last 50 years, crystallinity and capacity to generate free radicals have been recognized as relevant features for silica toxicity. The 'surface' also plays an important role in silica toxicity, but this term has often been used in a very general way, without defining which properties of the surface are actually driving toxicity. How the chemical features (e.g., silanols and siloxanes) and configuration of the silica surface can trigger toxic responses remains incompletely understood. MAIN BODY Recent developments in surface chemistry, cell biology and toxicology provide new avenues to improve our understanding of the molecular mechanisms of the adverse responses to silica particles. New physico-chemical methods can finely characterize and quantify silanols at the surface of silica particles. Advanced computational modelling and atomic force microscopy offer unique opportunities to explore the intimate interactions between silica surface and membrane models or cells. In recent years, interdisciplinary research, using these tools, has built increasing evidence that surface silanols are critical determinants of the interaction between silica particles and biomolecules, membranes, cell systems, or animal models. It also has become clear that silanol configuration, and eventually biological responses, can be affected by impurities within the crystal structure, or coatings covering the particle surface. The discovery of new molecular targets of crystalline as well as amorphous silica particles in the immune system and in epithelial lung cells represents new possible toxicity pathways. Cellular recognition systems that detect specific features of the surface of silica particles have been identified. CONCLUSIONS Interdisciplinary research bridging surface chemistry to toxicology is progressively solving the puzzling issue of the variable toxicity of silica. Further interdisciplinary research is ongoing to elucidate the intimate mechanisms of silica pathogenicity, to possibly mitigate or reduce surface reactivity.
Collapse
Affiliation(s)
- Cristina Pavan
- UCLouvain, Louvain centre for Toxicology and Applied Pharmacology (LTAP), Brussels, Belgium
| | - Massimo Delle Piane
- Bremen Center for Computational Material Science (BCCMS), Center for Environmental Research and Sustainable Technology (UFT), University of Bremen, Bremen, Germany
| | | | | | - Bice Fubini
- G. Scansetti Center, University of Torino, Turin, Italy
| | - Peter Hoet
- Department of Public Health and Primary Care, KU Leuven, Laboratory of Toxicology, Unit of Environment and Health, Leuven, Belgium
| | - Claire J. Horwell
- Institute of Hazard, Risk and Resilience, Department of Earth Sciences, Durham University, Durham, UK
| | - François Huaux
- UCLouvain, Louvain centre for Toxicology and Applied Pharmacology (LTAP), Brussels, Belgium
| | - Dominique Lison
- UCLouvain, Louvain centre for Toxicology and Applied Pharmacology (LTAP), Brussels, Belgium
| | - Cristina Lo Giudice
- UCLouvain, Institute of Biomolecular Science and Technology, NanoBioPhysics, Louvain-la-Neuve, Belgium
| | - Gianmario Martra
- Department of Chemistry and Nanostructured Interfaces and Surfaces –NIS Centre, University of Torino, Turin, Italy
| | - Eliseo Montfort
- Instituto de Tecnología Cerámica, Universitat Jaume I, Castellón, Spain
| | - Roel Schins
- IUF Leibniz Research Institute for Environmental Medicine, Düsseldorf, Germany
| | | | | | - Michelle Wyart-Remy
- EUROSIL, European Association of industrial silica producers, Brussels, Belgium
| | - Christina Ziemann
- Fraunhofer Institute for Toxicology and Experimental Medicine, ITEM, Hannover, Germany
| | - Francesco Turci
- Department of Chemistry, G. Scansetti Center, University of Torino, Turin, Italy
| |
Collapse
|
|
39
|
Helou DG, Martin SF, Pallardy M, Chollet-Martin S, Kerdine-Römer S. Nrf2 Involvement in Chemical-Induced Skin Innate Immunity. Front Immunol 2019; 10:1004. [PMID: 31134077 PMCID: PMC6514534 DOI: 10.3389/fimmu.2019.01004] [Citation(s) in RCA: 53] [Impact Index Per Article: 8.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/23/2018] [Accepted: 04/18/2019] [Indexed: 12/21/2022] Open
Abstract
Exposure to certain chemicals disturbs skin homeostasis. In particular, protein-reactive chemical contact sensitizers trigger an inflammatory immune response resulting in eczema and allergic contact dermatitis. Chemical sensitizers activate innate immune cells which orchestrate the skin immune response. This involves oxidative and inflammatory pathways. In parallel, the Nrf2/Keap1 pathway, a major ubiquitous regulator of cellular oxidative and electrophilic stress is activated in the different skin innate immune cells including epidermal Langerhans cells and dermal dendritic cells, but also in keratinocytes. In this context, Nrf2 shows a strong protective capacity through the downregulation of both the oxidative stress and inflammatory pathways. In this review we highlight the important role of Nrf2 in the control of the innate immune response of the skin to chemical sensitizers.
Collapse
Affiliation(s)
- Doumet Georges Helou
- Inflammation, Chimiokines et Immunopathologie, INSERM UMR996, University Paris-Sud, Université Paris-Saclay, Châtenay-Malabry, France
| | - Stefan F Martin
- Allergy Research Group, Department of Dermatology, Faculty of Medicine, University of Freiburg, Freiburg, Germany
| | - Marc Pallardy
- Inflammation, Chimiokines et Immunopathologie, INSERM UMR996, University Paris-Sud, Université Paris-Saclay, Châtenay-Malabry, France
| | - Sylvie Chollet-Martin
- Inflammation, Chimiokines et Immunopathologie, INSERM UMR996, University Paris-Sud, Université Paris-Saclay, Châtenay-Malabry, France.,UF Auto-immunité et Hypersensibilités, Hôpital Bichat, APHP, Paris, France
| | - Saadia Kerdine-Römer
- Inflammation, Chimiokines et Immunopathologie, INSERM UMR996, University Paris-Sud, Université Paris-Saclay, Châtenay-Malabry, France
| |
Collapse
|
|
40
|
Açaí (Euterpe oleracea Mart.) has anti-inflammatory potential through NLRP3-inflammasome modulation. J Funct Foods 2019. [DOI: 10.1016/j.jff.2019.03.034] [Citation(s) in RCA: 19] [Impact Index Per Article: 3.2] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/16/2022] Open
|
|
41
|
Cox LA(T. Risk Analysis Implications of Dose-Response Thresholds for NLRP3 Inflammasome-Mediated Diseases: Respirable Crystalline Silica and Lung Cancer as an Example. Dose Response 2019; 17:1559325819836900. [PMID: 31168301 PMCID: PMC6484684 DOI: 10.1177/1559325819836900] [Citation(s) in RCA: 11] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/07/2018] [Revised: 02/16/2019] [Accepted: 02/19/2019] [Indexed: 12/30/2022] Open
Abstract
Chronic inflammation mediates an extraordinarily wide range of diseases. Recent progress in understanding intracellular inflammasome assembly, priming, activation, cytokine signaling, and interactions with mitochondrial reactive oxygen species, lysosome disruption, cell death, and prion-like polymerization and spread of inflammasomes among cells, has potentially profound implications for dose-response modeling. This article discusses mechanisms of exposure concentration and duration thresholds for NOD-like receptor protein 3 (NLRP3)-mediated inflammatory responses and develops a simple biomathematical model of the onset of exposure-related tissue-level chronic inflammation and resulting disease risks, focusing on respirable crystalline silica (RCS) and lung cancer risk as an example. An inflammation-mediated 2-stage clonal expansion model of RCS-induced lung cancer is proposed that explains why relatively low estimated concentrations of RCS (eg, <1 mg/m3) do not increase lung cancer risk and why even high occupational concentrations increase risk only modestly (typically relative risk <2). The model of chronic inflammation implies a dose-response threshold for excess cancer risk, in contrast to traditional linear-no-threshold assumptions. If this implication is correct, then concentrations of crystalline silica (or amphibole asbestos fibers, or other environmental challenges that act via the NLRP3 inflammasome) below the threshold do not cause chronic inflammation and resulting elevated risks of inflammation-mediated diseases.
Collapse
|
|
42
|
Rothen-Rutishauser B, Bourquin J, Petri-Fink A. Nanoparticle-Cell Interactions: Overview of Uptake, Intracellular Fate and Induction of Cell Responses. BIOLOGICAL RESPONSES TO NANOSCALE PARTICLES 2019. [DOI: 10.1007/978-3-030-12461-8_6] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 01/18/2023]
|
|
43
|
Huaux F. Emerging Role of Immunosuppression in Diseases Induced by Micro- and Nano-Particles: Time to Revisit the Exclusive Inflammatory Scenario. Front Immunol 2018; 9:2364. [PMID: 30510551 PMCID: PMC6252316 DOI: 10.3389/fimmu.2018.02364] [Citation(s) in RCA: 23] [Impact Index Per Article: 3.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/04/2018] [Accepted: 09/24/2018] [Indexed: 12/21/2022] Open
Abstract
Fibrosis, cancer, and autoimmunity developing upon particle exposure have been exclusively linked with uncontrolled inflammatory processes. The critical role of inflammation is now challenged by several contradictory observations indicating that the emergence of these chronic disorders may result from non-inflammatory events. A growing number of studies reveals that micro- and nano-particles can cause exaggerated and persistent immunosuppression characterized by the release of potent anti-inflammatory cytokines (IL-10 and TGF-β), and the recruitment of major regulatory immune cells (M2 macrophages, T and B regs, and MDSC). This persistent immunosuppressive environment is initially established to limit early inflammation but contributes later to fibrosis, cancer, and infection. Immunosuppression promotes fibroblast proliferation and matrix element synthesis and subverts innate and adaptive immune surveillance against tumor cells and microorganisms. This review details the contribution of immunosuppressive cells and their derived immunoregulatory mediators and delineates the mutual role of inflammatory vs. immunosuppressive mechanisms in the pathogenesis of chronic diseases induced by particles. The consideration of these new results explains how particle-related diseases can develop independently of chronic inflammation, enriches current bioassays predicting particle toxicity and suggests new clinical strategies for treating patients affected by particle-associated diseases.
Collapse
Affiliation(s)
- François Huaux
- Louvain Centre for Toxicology and Applied Pharmacology, Institut de Recherche Experimentale et Clinique, Université catholique de Louvain, Brussels, Belgium
| |
Collapse
|
|
44
|
Shirasuna K, Karasawa T, Takahashi M. Exogenous nanoparticles and endogenous crystalline molecules as danger signals for the NLRP3 inflammasomes. J Cell Physiol 2018; 234:5436-5450. [PMID: 30370619 DOI: 10.1002/jcp.27475] [Citation(s) in RCA: 39] [Impact Index Per Article: 5.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/16/2018] [Accepted: 09/04/2018] [Indexed: 12/14/2022]
Abstract
Inflammasome mechanisms are involved as some of the pathways of sterile inflammation. Inflammasomes are large multiprotein complexes in the cytosol and are a key system for the production of the pivotal inflammatory cytokines, interleukin (IL)-1β and IL-18, and inflammatory cell death called pyroptosis. Although a number of inflammasomes have been described, the nucleotide-binding oligomerization domain-, leucine-rich repeat-, and pyrin domain-containing 3 (NLRP3) is the most extensively investigated inflammasome. Exogenous pathogen-associated molecular patterns released during infection and endogenous crystalline danger/damage-associated molecular patterns (DAMPs) are well-known activators of NLRP3 inflammasomes. In addition, nanoparticle-associated molecular patterns (NAMPs), which are mediated by synthetic materials, including nanomaterials and nanoparticles, are proposed to be new danger signals of NLRP3 inflammasomes. Importantly, NAMP- and DAMP-triggered inflammation, a defining characteristic in inflammatory diseases, is termed as sterile inflammation because it occurs in the absence of foreign pathogens. This review focuses on the role of inflammasomes in exogenous NAMP- and endogenous crystalline DAMP-mediated sterile inflammation. Moreover, many regulatory mechanisms have been identified to attenuate NLRP3 inflammasomes. Therefore, we also summarize endogenous negative regulators of NLRP3 inflammasome activation, particularly induced by NAMPs or crystalline DAMPs.
Collapse
Affiliation(s)
- Koumei Shirasuna
- Department of Animal Science, Tokyo University of Agriculture, Japan
| | - Tadayoshi Karasawa
- Division of Inflammation Research, Center for Molecular Medicine, Jichi Medical University, Japan
| | - Masafumi Takahashi
- Division of Inflammation Research, Center for Molecular Medicine, Jichi Medical University, Japan
| |
Collapse
|
|
45
|
Leso V, Fontana L, Iavicoli I. Nanomaterial exposure and sterile inflammatory reactions. Toxicol Appl Pharmacol 2018; 355:80-92. [DOI: 10.1016/j.taap.2018.06.021] [Citation(s) in RCA: 19] [Impact Index Per Article: 2.7] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/11/2018] [Revised: 06/24/2018] [Accepted: 06/25/2018] [Indexed: 12/20/2022]
|
|
46
|
Li C, Zhang P, Hao Y, He D, Shen Y, Lu R. Expression and significance of quantum dots in RAW 264.7 macrophages. Oncol Lett 2018; 16:5997-6002. [PMID: 30333871 DOI: 10.3892/ol.2018.9362] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/17/2017] [Accepted: 04/23/2018] [Indexed: 12/29/2022] Open
Abstract
The aim of the present study was to investigate the clinical application and utility of CdSe/ZnS quantum dots (QDs) in tracing RAW 264.7 macrophages. RAW 264.7 cells and QDs at various concentrations were co-cultured for 24 h, and the fluorescence intensity of the macrophages was determined at various time points. The mRNA expression levels of genes encoding inflammatory cytokines [tumor necrosis factor (TNF)-α and interleukin (IL)-1β] were determined, and cellular assays were performed to investigate the activation, proliferation and apoptosis of RAW 264.7 cells. The QDs were engulfed by the macrophages, and the fluorescence intensity of RAW 264.7 cells increased with increasing concentration and time. The IL-1β mRNA level increased significantly at 50 µg/ml QDs, and that of TNF-α increased significantly at 100 µg/ml QDs. Accelerated proliferation of RAW 264.7 cells was observed at 50 and 100 µg/ml QDs; however, no increase in apoptosis of RAW 264.7 cells was observed in co-culture. CdSe/ZnS QDs may be used as tracers due to the fluorescence intensity of RAW 264.7 cells increasing with increasing QD concentration and time, resulting in the activation of macrophages and significant increases in proliferation at 50 and 100 µg/ml QDs compared with in the absence of QDs. The change in QD concentration was not significantly associated with the proliferation and apoptosis of RAW 264.7 macrophages.
Collapse
Affiliation(s)
- Chong Li
- Department of Orthopedics, The First People's Hospital of Kunshan, Jiangsu University, Kunshan, Jiangsu 215300, P.R. China
| | - Panpan Zhang
- Department of Laboratory, The First People's Hospital of Kunshan, Jiangsu University, Kunshan, Jiangsu 215300, P.R. China
| | - Yanming Hao
- Department of Orthopedics, The First People's Hospital of Kunshan, Jiangsu University, Kunshan, Jiangsu 215300, P.R. China
| | - Dawei He
- Department of Laboratory, The First People's Hospital of Kunshan, Jiangsu University, Kunshan, Jiangsu 215300, P.R. China
| | - Yixin Shen
- Department of Orthopedics, The Second Affiliated Hospital of Soochow University, Suzhou, Jiangsu 215004, P.R. China
| | - Rongzhu Lu
- Laboratory Center, The First People's Hospital of Kunshan, Jiangsu University, Kunshan, Jiangsu 215300, P.R. China
| |
Collapse
|
|
47
|
Chen L, Liu J, Zhang Y, Zhang G, Kang Y, Chen A, Feng X, Shao L. The toxicity of silica nanoparticles to the immune system. Nanomedicine (Lond) 2018; 13:1939-1962. [PMID: 30152253 DOI: 10.2217/nnm-2018-0076] [Citation(s) in RCA: 166] [Impact Index Per Article: 23.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/07/2023] Open
Abstract
Silicon-based materials and their oxides are widely used in drug delivery, dietary supplements, implants and dental fillers. Silica nanoparticles (SiNPs) interact with immunocompetent cells and induce immunotoxicity. However, the toxic effects of SiNPs on the immune system have been inadequately reviewed. The toxicity of SiNPs to the immune system depends on their physicochemical properties and the cell type. Assessments of immunotoxicity include determining cell dysfunctions, cytotoxicity and genotoxicity. This review focuses on the immunotoxicity of SiNPs and investigates the underlying mechanisms. The main mechanisms were proinflammatory responses, oxidative stress and autophagy. Considering the toxicity of SiNPs, surface and shape modifications may mitigate the toxic effects of SiNPs, providing a new way to produce these nanomaterials with less toxic impaction.
Collapse
Affiliation(s)
- Liangjiao Chen
- Key Laboratory of Oral Medicine, Guangzhou Institute of Oral Disease, Stomatology Hospital of Guangzhou Medical University, Guangzhou 510140, PR China
| | - Jia Liu
- Nanfang Hospital, Southern Medical University, Guangzhou 510515, PR China
| | - Yanli Zhang
- Nanfang Hospital, Southern Medical University, Guangzhou 510515, PR China
| | - Guilan Zhang
- Nanfang Hospital, Southern Medical University, Guangzhou 510515, PR China
| | - Yiyuan Kang
- Nanfang Hospital, Southern Medical University, Guangzhou 510515, PR China
| | - Aijie Chen
- Nanfang Hospital, Southern Medical University, Guangzhou 510515, PR China
| | - Xiaoli Feng
- Nanfang Hospital, Southern Medical University, Guangzhou 510515, PR China
| | - Longquan Shao
- Nanfang Hospital, Southern Medical University, Guangzhou 510515, PR China
| |
Collapse
|
|
48
|
Innate immunity to inhaled particles: A new paradigm of collective recognition. CURRENT OPINION IN TOXICOLOGY 2018. [DOI: 10.1016/j.cotox.2018.02.004] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/15/2022]
|
|
49
|
Zhang Y, Feng J, Fu H, Liu C, Yu Z, Sun Y, She X, Li P, Zhao C, Liu Y, Liu T, Liu Q, Liu Q, Li G, Wu M. Coagulation Factor X Regulated by CASC2c Recruited Macrophages and Induced M2 Polarization in Glioblastoma Multiforme. Front Immunol 2018; 9:1557. [PMID: 30034397 PMCID: PMC6043648 DOI: 10.3389/fimmu.2018.01557] [Citation(s) in RCA: 44] [Impact Index Per Article: 6.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/21/2018] [Accepted: 06/25/2018] [Indexed: 12/18/2022] Open
Abstract
Tumor-associated macrophages (TAMs) constitute a major component of inflammatory cells in the glioblastoma multiforme (GBM) tumor microenvironment. TAMs have been implicated in GBM angiogenesis, invasion, local tumor recurrence, and immunosuppression. Coagulation factor X (FX) is a vitamin K-dependent plasma protein that plays a role in the regulation of blood coagulation. In this study, we first found that FX was highly expressed and positively correlated with TAM density in human GBM. FX exhibited a potent chemotactic capacity to recruit macrophages and promoted macrophages toward M2 subtype polarization, accelerating GBM growth. FX bound to extracellular signal-related kinase (ERK)1/2 and inhibited p-ERK1/2 in GBM cells. FX was secreted in the tumor microenvironment and increased the phosphorylation and activation of ERK1/2 and AKT in macrophages, which may have been responsible for the M2 subtype macrophage polarization. Moreover, although the lncRNA CASC2c has been verified to function as a miR-101 competing endogenous RNA (ceRNA) to promote miR-101 target genes in GBM cells, we first confirmed that CASC2c did not function as a miR-338-3p ceRNA to promote FX expression, and that FX was a target gene of miR-338-3p. CASC2c interacted with and reciprocally repressed miR-338-3p. Both CASC2c and miR-388-3p bound to FX and commonly inhibited its expression and secretion. CASC2c repressed M2 subtype macrophage polarization. Taken together, our findings revealed a novel mechanism highlighting CASC2c and FX as potential therapeutic targets to improve GBM patients by altering the GBM microenvironment.
Collapse
Affiliation(s)
- Yan Zhang
- Hunan Provincial Tumor Hospital and the Affiliated Tumor Hospital of Xiangya Medical School, Central South University, Changsha, China.,The Key Laboratory of Carcinogenesis of the Chinese Ministry of Health, The Key Laboratory of Carcinogenesis and Cancer Invasion of the Chinese Ministry of Education, Cancer Research Institute, Central South University, Changsha, China
| | - Jianbo Feng
- Hunan Provincial Tumor Hospital and the Affiliated Tumor Hospital of Xiangya Medical School, Central South University, Changsha, China.,The Key Laboratory of Carcinogenesis of the Chinese Ministry of Health, The Key Laboratory of Carcinogenesis and Cancer Invasion of the Chinese Ministry of Education, Cancer Research Institute, Central South University, Changsha, China
| | - Haijuan Fu
- Hunan Provincial Tumor Hospital and the Affiliated Tumor Hospital of Xiangya Medical School, Central South University, Changsha, China.,The Key Laboratory of Carcinogenesis of the Chinese Ministry of Health, The Key Laboratory of Carcinogenesis and Cancer Invasion of the Chinese Ministry of Education, Cancer Research Institute, Central South University, Changsha, China
| | - Changhong Liu
- Hunan Provincial Tumor Hospital and the Affiliated Tumor Hospital of Xiangya Medical School, Central South University, Changsha, China.,The Key Laboratory of Carcinogenesis of the Chinese Ministry of Health, The Key Laboratory of Carcinogenesis and Cancer Invasion of the Chinese Ministry of Education, Cancer Research Institute, Central South University, Changsha, China
| | - Zhibin Yu
- Hunan Provincial Tumor Hospital and the Affiliated Tumor Hospital of Xiangya Medical School, Central South University, Changsha, China.,The Key Laboratory of Carcinogenesis of the Chinese Ministry of Health, The Key Laboratory of Carcinogenesis and Cancer Invasion of the Chinese Ministry of Education, Cancer Research Institute, Central South University, Changsha, China
| | - Yingnan Sun
- Hunan Provincial Tumor Hospital and the Affiliated Tumor Hospital of Xiangya Medical School, Central South University, Changsha, China
| | - Xiaoling She
- The Second Xiangya Hospital, Central South University, Changsha, China
| | - Peiyao Li
- Hunan Provincial Tumor Hospital and the Affiliated Tumor Hospital of Xiangya Medical School, Central South University, Changsha, China.,The Key Laboratory of Carcinogenesis of the Chinese Ministry of Health, The Key Laboratory of Carcinogenesis and Cancer Invasion of the Chinese Ministry of Education, Cancer Research Institute, Central South University, Changsha, China
| | - Chunhua Zhao
- Hunan Provincial Tumor Hospital and the Affiliated Tumor Hospital of Xiangya Medical School, Central South University, Changsha, China.,The Key Laboratory of Carcinogenesis of the Chinese Ministry of Health, The Key Laboratory of Carcinogenesis and Cancer Invasion of the Chinese Ministry of Education, Cancer Research Institute, Central South University, Changsha, China
| | - Yang Liu
- Hunan Provincial Tumor Hospital and the Affiliated Tumor Hospital of Xiangya Medical School, Central South University, Changsha, China.,The Key Laboratory of Carcinogenesis of the Chinese Ministry of Health, The Key Laboratory of Carcinogenesis and Cancer Invasion of the Chinese Ministry of Education, Cancer Research Institute, Central South University, Changsha, China
| | - Tao Liu
- Hunan Provincial Tumor Hospital and the Affiliated Tumor Hospital of Xiangya Medical School, Central South University, Changsha, China.,The Key Laboratory of Carcinogenesis of the Chinese Ministry of Health, The Key Laboratory of Carcinogenesis and Cancer Invasion of the Chinese Ministry of Education, Cancer Research Institute, Central South University, Changsha, China
| | - Qiang Liu
- The Third Xiangya Hospital, Central South University, Changsha, China
| | - Qing Liu
- The Xiangya Hospital, Central South University, Changsha, China
| | - Guiyuan Li
- Hunan Provincial Tumor Hospital and the Affiliated Tumor Hospital of Xiangya Medical School, Central South University, Changsha, China.,The Key Laboratory of Carcinogenesis of the Chinese Ministry of Health, The Key Laboratory of Carcinogenesis and Cancer Invasion of the Chinese Ministry of Education, Cancer Research Institute, Central South University, Changsha, China
| | - Minghua Wu
- Hunan Provincial Tumor Hospital and the Affiliated Tumor Hospital of Xiangya Medical School, Central South University, Changsha, China.,The Key Laboratory of Carcinogenesis of the Chinese Ministry of Health, The Key Laboratory of Carcinogenesis and Cancer Invasion of the Chinese Ministry of Education, Cancer Research Institute, Central South University, Changsha, China
| |
Collapse
|
|
50
|
Zhao F, Wang C, Yang Q, Han S, Hu Q, Fu Z. Titanium dioxide nanoparticle stimulating pro-inflammatory responses in vitro and in vivo for inhibited cancer metastasis. Life Sci 2018; 202:44-51. [PMID: 29625194 DOI: 10.1016/j.lfs.2018.03.058] [Citation(s) in RCA: 14] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/02/2018] [Revised: 03/19/2018] [Accepted: 03/29/2018] [Indexed: 01/07/2023]
Abstract
AIMS The interaction of engineered nanoparticles (NPs) with the immune system and the possibility of inflammation induction are of particularly interest. Titanium dioxide nanoparticles (TiO2 NPs) are one of the most popular manufactured nanomaterials. In this study, we focused on the immune-modulatory effect of commercial P-25 TiO2 NPs in vivo and in vitro and their crucial role in cancer metastasis. MAIN METHODS The female C57BL/6 mice were injected into abdominal cavity with PBS or P-25 TiO2 to investigate the immune-modulatory function of P-25. And breast cancer cells were intravenously (i.v.) injected into mouse to establish the liver and lung cancer metastasis model. Peritoneal macrophage was used to investigate the macrophage polarization in vitro. KEY FINDINGS Results showed us that peritoneal macrophage exposed to P-25 TiO2 NPs displayed activated M1 macrophage response, as evidenced by the increased mRNA expression of interleukin-1β (IL1β), IL6, TNFα, CCR7 and inducible nitric oxide synthase (iNOS). After exposure of TiO2 NPs in vivo for 21 days, the body weights of mice decreased significantly, which were accompanied by an infiltration of immune cells in liver and spleen in 20 mg/kg BW treated group. Importantly, the production of pro-inflammatory cytokines in liver, spleen and the serum were amplified, which indicated the tissue and systemic inflammation induced by TiO2 NPs. In addition, the activation of immune response induced by P-25 TiO2 NPs was correlated with their ability to inhibit cancer metastasis. SIGNIFICANCE Our results delineated the stimulating pro-inflammatory response induced by P-25 TiO2 NPs and their outcome in vivo for cancer metastasis.
Collapse
Affiliation(s)
- Fenghui Zhao
- College of Biotechnology and Bioengineering, Zhejiang University of Technology, China
| | - Chengcheng Wang
- College of Biotechnology and Bioengineering, Zhejiang University of Technology, China
| | - Qiaolei Yang
- College of Biotechnology and Bioengineering, Zhejiang University of Technology, China
| | - Shuhong Han
- College of Biotechnology and Bioengineering, Zhejiang University of Technology, China
| | - Qinglian Hu
- College of Biotechnology and Bioengineering, Zhejiang University of Technology, China.
| | - Zhengwei Fu
- College of Biotechnology and Bioengineering, Zhejiang University of Technology, China.
| |
Collapse
|