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Song Q, Xu P, Xiao Q, Zhang C, Mao Y. Crosstalk between white adipose tissue and skin: Unraveling its role in psoriasis pathogenesis (Review). Mol Med Rep 2025; 31:169. [PMID: 40242953 PMCID: PMC12012418 DOI: 10.3892/mmr.2025.13534] [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: 12/18/2024] [Accepted: 04/02/2025] [Indexed: 04/18/2025] Open
Abstract
Psoriasis is a chronic systemic inflammatory skin disorder characterized by hyperproliferation of keratinocytes and significant immune dysregulation. Obesity is markedly associated with psoriasis, acting as an independent risk factor that exacerbates disease severity and treatment failure, while weight‑reduction interventions can improve psoriatic lesions. However, the mechanisms by which obesity promotes the onset and progression of psoriatic lesions still require further elucidation. The present comprehensive narrative review highlighted the critical role of the crosstalk between white adipose tissue (WAT) and skin in the pathogenesis of psoriasis. The expansion of WAT contributes to inflammation, epidermal proliferation and angiogenesis in skin lesions through the release of adipokines, extracellular vesicles and free fatty acids. Conversely, psoriatic lesions induce dysregulation in the inflammation and function of WAT. These findings suggested that this bidirectional communication not only explains the high prevalence of obesity among patients with psoriasis, but also highlights the importance of addressing metabolic comorbidities in treatment strategies.
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Affiliation(s)
- Qiuhe Song
- Department of Dermatology, Affiliated Hospital of Jiujiang University, Jiujiang, Jiangxi 332000, P.R. China
| | - Pengfei Xu
- Department of Dermatology, Affiliated Hospital of Jiujiang University, Jiujiang, Jiangxi 332000, P.R. China
| | - Qipeng Xiao
- Department of Dermatology, Affiliated Hospital of Jiujiang University, Jiujiang, Jiangxi 332000, P.R. China
| | - Chaowen Zhang
- Department of Dermatology, Affiliated Hospital of Jiujiang University, Jiujiang, Jiangxi 332000, P.R. China
| | - Yousheng Mao
- Department of Dermatology, Affiliated Hospital of Jiujiang University, Jiujiang, Jiangxi 332000, P.R. China
- Jiujiang Clinical Precision Medicine Research Center, Affiliated Hospital of Jiujiang University, Jiujiang, Jiangxi 332000, P.R. China
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Shang D, Zhao S. Molecular mechanisms of obesity predisposes to atopic dermatitis. Front Immunol 2024; 15:1473105. [PMID: 39564133 PMCID: PMC11574713 DOI: 10.3389/fimmu.2024.1473105] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/30/2024] [Accepted: 10/15/2024] [Indexed: 11/21/2024] Open
Abstract
Obesity is a prevalent metabolic disease that reduces bacterial diversity, colonizes the epidermis with lipophilic bacteria, and increases intestinal pro-inflammatory species, all of which lead to impaired epithelial barriers. Adipose tissue secretes immunomodulatory molecules, such as adipokines, leptin, and adiponectin, which alters the morphology of adipocytes and macrophages as well as modulates T cell differentiation and peripheral Th2-dominated immune responses. Atopic dermatitis (AD) and obesity have similar pathological manifestations, including inflammation as well as insulin and leptin resistance. This review examines the major mechanisms between obesity and AD, which focus on the effect on skin and gut microbiota, immune responses mediated by the toll like receptor (TLR) signaling pathway, and changes in cytokine levels (TNF-a, IL-6, IL-4, and IL13). Moreover, we describe the potential effects of adipokines on AD and finally mechanisms by which PPAR-γ suppresses and regulates type 2 immunity.
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Affiliation(s)
- Dajin Shang
- School of China Medical University, Shenyang, Liaoning, China
| | - Shengnan Zhao
- School of China Medical University, Shenyang, Liaoning, China
- Department of Dermatology, The First Hospital of China Medical University, Shenyang, China
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Yu JE, Jeon SH, Kim MJ, Kim DH, Koo JK, Kim TH, Kim B, Yoon JY, Lim YS, Park SR, Yeo IJ, Yun J, Son DJ, Han SB, Lee YS, Hong JT. Anti-chitinase-3-like 1 antibody attenuated atopic dermatitis-like skin inflammation through inhibition of STAT3-dependent CXCL8 expression. Br J Pharmacol 2024; 181:3232-3245. [PMID: 38745399 DOI: 10.1111/bph.16365] [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: 09/02/2023] [Revised: 01/27/2024] [Accepted: 02/02/2024] [Indexed: 05/16/2024] Open
Abstract
BACKGROUND AND PURPOSE Chitinase-3-like 1 (CHI3L1) causes skin inflammation in the progression of atopic dermatitis. We investigated if anti-CHI3L1 antibody could prevent the development of atopic dermatitis and its mechanisms of action. EXPERIMENTAL APPROACH The effect of CHI3L1 antibody on phthalic anhydride-induced atopic dermatitis animal model and in vitro reconstructed human skin (RHS) model were investigated. Expression and release of atopic dermatitis-related cytokines were determined using an enzyme-linked immunosorbent assay, and RT-qPCR, STAT3 and CXCL8 signalling were measured by western blotting. KEY RESULTS Anti-CHI3L1 antibody suppressed phthalic anhydride-induced epidermal thickening, clinical score, IgE level and infiltration of inflammatory cells, and reduced phthalic anhydride-induced inflammatory cytokines concentration. In addition, CHI3L1 antibody treatment inhibited the expression of STAT3 activity in phthalic anhydride-treated skin. It was also confirmed that CHI3L1 antibody treatment alleviated atopic dermatitis-related inflammation in the RHS model. The inhibitory effects of CHI3L1 antibody was similar or more effective compared with that of the IL-4 antibody. We further found that CHI3L1 is associated with CXCL8 by protein-association network analysis. siRNA of CHI3L1 blocked the mRNA levels of CHI3L1, IL-1β, IL-4, CXCL8, TSLP, and the expression of CHI3L1 and p-STAT, and the level of CXCL8, whereas recombinant level of CXCL8 was elevated. Moreover, siRNA of STAT3 reduced the mRNA level of these cytokines. CHI3L1 and p-STAT3 expression correlated with the reduced CXCL8 level in the RHS in vitro model. CONCLUSION AND IMPLICATIONS Our data demonstrated that CHI3L1 antibody could be a promising effective therapeutic drug for atopic dermatitis.
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Affiliation(s)
- Ji Eun Yu
- College of Pharmacy and Medical Research Center, Chungbuk National University, Cheongju-si, Chungbuk, Republic of Korea
- College of Pharmacy, Mokpo National University, Muan-gun, Jeonnam, Republic of Korea
| | - Seong Hee Jeon
- College of Pharmacy and Medical Research Center, Chungbuk National University, Cheongju-si, Chungbuk, Republic of Korea
| | - Min Ji Kim
- College of Pharmacy and Medical Research Center, Chungbuk National University, Cheongju-si, Chungbuk, Republic of Korea
| | - Dae Hwan Kim
- College of Pharmacy and Medical Research Center, Chungbuk National University, Cheongju-si, Chungbuk, Republic of Korea
| | - Ja Keun Koo
- College of Pharmacy and Medical Research Center, Chungbuk National University, Cheongju-si, Chungbuk, Republic of Korea
| | - Tae Hun Kim
- Autotelic Bio Inc., Cheongju-si, Chungbuk, Republic of Korea
| | - Bongcheol Kim
- Senelix Co. Ltd., Songpa-gu, Seoul, Republic of Korea
| | - Ji Yong Yoon
- PRESTI GEBIOLOGICS Co. Ltd., Cheongju-si, Chungbuk, Republic of Korea
| | - Young-Soo Lim
- PRESTI GEBIOLOGICS Co. Ltd., Cheongju-si, Chungbuk, Republic of Korea
| | - So Ra Park
- New Drug Development Center, Osong Medical Innovation Foundation, Cheongju-si, Chungcheongbuk-do, Korea
| | - In Jun Yeo
- College of Pharmacy and Medical Research Center, Chungbuk National University, Cheongju-si, Chungbuk, Republic of Korea
- College of Pharmacy, Kyungpook National University, Buk-gu, Daegu, Republic of Korea
| | - Jaesuk Yun
- College of Pharmacy and Medical Research Center, Chungbuk National University, Cheongju-si, Chungbuk, Republic of Korea
| | - Dong Ju Son
- College of Pharmacy and Medical Research Center, Chungbuk National University, Cheongju-si, Chungbuk, Republic of Korea
| | - Sang-Bae Han
- College of Pharmacy and Medical Research Center, Chungbuk National University, Cheongju-si, Chungbuk, Republic of Korea
| | - Yong Sun Lee
- College of Pharmacy and Medical Research Center, Chungbuk National University, Cheongju-si, Chungbuk, Republic of Korea
| | - Jin Tae Hong
- College of Pharmacy and Medical Research Center, Chungbuk National University, Cheongju-si, Chungbuk, Republic of Korea
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Scala E, Mercurio L, Albanesi C, Madonna S. The Intersection of the Pathogenic Processes Underlying Psoriasis and the Comorbid Condition of Obesity. Life (Basel) 2024; 14:733. [PMID: 38929716 PMCID: PMC11204971 DOI: 10.3390/life14060733] [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: 04/15/2024] [Revised: 05/20/2024] [Accepted: 06/04/2024] [Indexed: 06/28/2024] Open
Abstract
In the past decade, our understanding of psoriasis pathogenesis has made significant steps forward, leading to the development of multiple game-changing therapies. While psoriasis primarily affects the skin, it is increasingly recognized as a systemic disease that can have effects beyond the skin. Obesity is associated with more severe forms of psoriasis and can potentially worsen the systemic inflammation and metabolic dysfunction seen in psoriatic patients. The exact mechanisms underlying the link between these two conditions are not fully understood, but it is believed that chronic inflammation and immune dysregulation play a role. In this review, we examine the existing body of knowledge regarding the intersection of pathogenic processes responsible for psoriasis and obesity. The ability of biological therapies to reduce systemic and obesity-related inflammation in patients with psoriasis will be also discussed.
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Arroyo AB, Bernal-Carrión M, Cantón-Sandoval J, Cabas I, Corbalán-Vélez R, Martínez-Menchón T, Ferri B, Cayuela ML, García-Moreno D, Mulero V. NAMPT and PARylation Are Involved in the Pathogenesis of Atopic Dermatitis. Int J Mol Sci 2023; 24:ijms24097992. [PMID: 37175698 PMCID: PMC10178103 DOI: 10.3390/ijms24097992] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/03/2023] [Revised: 04/24/2023] [Accepted: 04/25/2023] [Indexed: 05/15/2023] Open
Abstract
Atopic dermatitis (AD) is a chronic inflammatory skin disease of very high prevalence, especially in childhood, with no specific treatment or cure. As its pathogenesis is complex, multifactorial and not fully understood, further research is needed to increase knowledge and develop new targeted therapies. We have recently demonstrated the critical role of NAD+ and poly (ADP-ribose) (PAR) metabolism in oxidative stress and skin inflammation. Specifically, we found that hyperactivation of PARP1 in response to DNA damage induced by reactive oxygen species, and fueled by NAMPT-derived NAD+, mediated inflammation through parthanatos cell death in zebrafish and human organotypic 3D skin models of psoriasis. Furthermore, the aberrant induction of NAMPT and PARP activity was observed in the lesional skin of psoriasis patients, supporting the role of these signaling pathways in psoriasis and pointing to NAMPT and PARP1 as potential novel therapeutic targets in treating skin inflammatory disorders. In the present work, we report, for the first time, altered NAD+ and PAR metabolism in the skin of AD patients and a strong correlation between NAMPT and PARP1 expression and the lesional status of AD. Furthermore, using a human 3D organotypic skin model of AD, we demonstrate that the pharmacological inhibition of NAMPT and PARP reduces pathology-associated biomarkers. These results help to understand the complexity of AD and reveal new potential treatments for AD patients.
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Affiliation(s)
- Ana B Arroyo
- Inmunidad, Inflamación y Cáncer, Departamento de Biología Celular e Histología, Facultad de Biología, Universidad de Murcia, 30100 Murcia, Spain
- Instituto Murciano de Investigación Biosanitaria (IMIB)-Pascual Parrilla, 30120 Murcia, Spain
- Centro de Investigación Biomédica en Red de Enfermedades Raras (CIBERER), Instituto de Salud Carlos III, 28029 Madrid, Spain
| | - Martín Bernal-Carrión
- Inmunidad, Inflamación y Cáncer, Departamento de Biología Celular e Histología, Facultad de Biología, Universidad de Murcia, 30100 Murcia, Spain
- Instituto Murciano de Investigación Biosanitaria (IMIB)-Pascual Parrilla, 30120 Murcia, Spain
| | - Joaquín Cantón-Sandoval
- Inmunidad, Inflamación y Cáncer, Departamento de Biología Celular e Histología, Facultad de Biología, Universidad de Murcia, 30100 Murcia, Spain
- Instituto Murciano de Investigación Biosanitaria (IMIB)-Pascual Parrilla, 30120 Murcia, Spain
- Centro de Investigación Biomédica en Red de Enfermedades Raras (CIBERER), Instituto de Salud Carlos III, 28029 Madrid, Spain
| | - Isabel Cabas
- Inmunidad, Inflamación y Cáncer, Departamento de Biología Celular e Histología, Facultad de Biología, Universidad de Murcia, 30100 Murcia, Spain
- Instituto Murciano de Investigación Biosanitaria (IMIB)-Pascual Parrilla, 30120 Murcia, Spain
- Centro de Investigación Biomédica en Red de Enfermedades Raras (CIBERER), Instituto de Salud Carlos III, 28029 Madrid, Spain
| | - Raúl Corbalán-Vélez
- Instituto Murciano de Investigación Biosanitaria (IMIB)-Pascual Parrilla, 30120 Murcia, Spain
- Hospital Clínico Universitario Virgen de la Arrixaca, 30120 Murcia, Spain
| | - Teresa Martínez-Menchón
- Instituto Murciano de Investigación Biosanitaria (IMIB)-Pascual Parrilla, 30120 Murcia, Spain
- Hospital Clínico Universitario Virgen de la Arrixaca, 30120 Murcia, Spain
| | - Belén Ferri
- Hospital Clínico Universitario Virgen de la Arrixaca, 30120 Murcia, Spain
| | - María L Cayuela
- Instituto Murciano de Investigación Biosanitaria (IMIB)-Pascual Parrilla, 30120 Murcia, Spain
- Centro de Investigación Biomédica en Red de Enfermedades Raras (CIBERER), Instituto de Salud Carlos III, 28029 Madrid, Spain
- Hospital Clínico Universitario Virgen de la Arrixaca, 30120 Murcia, Spain
| | - Diana García-Moreno
- Instituto Murciano de Investigación Biosanitaria (IMIB)-Pascual Parrilla, 30120 Murcia, Spain
- Centro de Investigación Biomédica en Red de Enfermedades Raras (CIBERER), Instituto de Salud Carlos III, 28029 Madrid, Spain
| | - Victoriano Mulero
- Inmunidad, Inflamación y Cáncer, Departamento de Biología Celular e Histología, Facultad de Biología, Universidad de Murcia, 30100 Murcia, Spain
- Instituto Murciano de Investigación Biosanitaria (IMIB)-Pascual Parrilla, 30120 Murcia, Spain
- Centro de Investigación Biomédica en Red de Enfermedades Raras (CIBERER), Instituto de Salud Carlos III, 28029 Madrid, Spain
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Kiełbowski K, Bakinowska E, Ostrowski P, Pala B, Gromowska E, Gurazda K, Dec P, Modrzejewski A, Pawlik A. The Role of Adipokines in the Pathogenesis of Psoriasis. Int J Mol Sci 2023; 24:ijms24076390. [PMID: 37047363 PMCID: PMC10094354 DOI: 10.3390/ijms24076390] [Citation(s) in RCA: 23] [Impact Index Per Article: 11.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/26/2023] [Revised: 03/24/2023] [Accepted: 03/27/2023] [Indexed: 03/31/2023] Open
Abstract
Psoriasis is a chronic and immune-mediated skin condition characterized by pro-inflammatory cytokines and keratinocyte hyperproliferation. Dendritic cells, T lymphocytes, and keratinocytes represent the main cell subtypes involved in the pathogenesis of psoriasis, while the interleukin-23 (IL-23)/IL-17 pathway enhances the disease progression. Human adipose tissue is an endocrine organ, which secretes multiple proteins, known as adipokines, such as adiponectin, leptin, visfatin, or resistin. Current evidence highlights the immunomodulatory roles of adipokines, which may contribute to the progression or suppression of psoriasis. A better understanding of the complexity of psoriasis pathophysiology linked with adipokines could result in developing novel diagnostic or therapeutic strategies. This review aims to present the pathogenesis of psoriasis and the roles of adipokines in this process.
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7
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Guan J, Wu C, He Y, Lu F. Skin-associated adipocytes in skin barrier immunity: A mini-review. Front Immunol 2023; 14:1116548. [PMID: 36761769 PMCID: PMC9902365 DOI: 10.3389/fimmu.2023.1116548] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/05/2022] [Accepted: 01/04/2023] [Indexed: 01/25/2023] Open
Abstract
The skin contributes critically to health via its role as a barrier tissue against a multitude of external pathogens. The barrier function of the skin largely depends on the uppermost epidermal layer which is reinforced by skin barrier immunity. The integrity and effectiveness of skin barrier immunity strongly depends on the close interplay and communication between immune cells and the skin environment. Skin-associated adipocytes have been recognized to play a significant role in modulating skin immune responses and infection by secreting cytokines, adipokines, and antimicrobial peptides. This review summarizes the recent understanding of the interactions between skin-associated adipocytes and other skin cells in maintaining the integrity and effectiveness of skin barrier immunity.
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Affiliation(s)
| | | | - Yunfan He
- *Correspondence: Feng Lu, ; Yunfan He,
| | - Feng Lu
- *Correspondence: Feng Lu, ; Yunfan He,
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8
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Visfatin Amplifies Cardiac Inflammation and Aggravates Cardiac Injury via the NF-κB p65 Signaling Pathway in LPS-Treated Mice. Mediators Inflamm 2022; 2022:3306559. [PMID: 36262545 PMCID: PMC9576419 DOI: 10.1155/2022/3306559] [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: 07/19/2022] [Revised: 08/09/2022] [Accepted: 09/08/2022] [Indexed: 11/18/2022] Open
Abstract
Background Visfatin is an adipocytokine that has been demonstrated to be involved in cardiovascular diseases. This study aims at determining the role of visfatin in sepsis-induced cardiac injury and identify its possible mechanisms. Methods Dynamic changes in visfatin expression in mice with lipopolysaccharide- (LPS-) induced septicemia were measured. Additionally, mice were pretreated with visfatin and further administered LPS to observe the effects of visfatin on cardiac injury. Finally, septic mice were also pretreated with JSH-23 to investigate whether visfatin regulates cardiac injury via the NF-κB p65 pathway. Results Visfatin expression levels in both the heart and serum were increased in LPS-treated mice and peaked at 6 hours, and visfatin was derived from cardiac macrophages. In septic mice, pretreatment with visfatin reduced the survival rate, worsened cardiac dysfunction, and increased the expression of cardiac injury markers, including creatine kinase myocardial bound (CK-MB) and lactate dehydrogenase (LDH). Treatment with visfatin also increased the infiltration of CD3+ cells and F4/80+ cells, amplified the cardiac inflammatory response, and elevated myocardial cell apoptosis. Treatment with JSH-23 reversed the effects of visfatin in septic mice. Conclusions This study showed that visfatin amplifies the cardiac inflammatory response and aggravates cardiac injury through the p65 signaling pathway. Visfatin may be a clinical target for preventing cardiac injury in sepsis.
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Nguyen LTH, Choi MJ, Shin HM, Yang IJ. Coptisine Alleviates Imiquimod-Induced Psoriasis-like Skin Lesions and Anxiety-like Behavior in Mice. Molecules 2022; 27:1412. [PMID: 35209199 PMCID: PMC8878104 DOI: 10.3390/molecules27041412] [Citation(s) in RCA: 16] [Impact Index Per Article: 5.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/04/2022] [Revised: 02/16/2022] [Accepted: 02/16/2022] [Indexed: 02/04/2023] Open
Abstract
Psoriasis is a common inflammatory skin disorder, which can be associated with psychological disorders, such as anxiety and depression. This study investigated the efficacy and the mechanism of action of a natural compound coptisine using imiquimod (IMQ)-induced psoriasis mice. Coptisine reduced the severity of psoriasis-like skin lesions, decreased epidermal hyperplasia and the levels of inflammatory cytokines TNF-α, IL-17, and IL-22. Furthermore, coptisine improved IMQ-induced anxiety in mice by increasing the number of entries and time in open arms in the elevated plus maze (EPM) test. Coptisine also lowered the levels of inflammatory cytokines TNF-α and IL-1β in the prefrontal cortex of psoriasis mice. HaCaT keratinocytes and BV2 microglial cells were used to investigate the effects of coptisine in vitro. In M5-treated HaCaT cells, coptisine decreased the production of IL-6, MIP-3α/CCL20, IP-10/CXCL10, and ICAM-1 and suppressed the NF-κB signaling pathway. In LPS-stimulated BV2 cells, coptisine reduced the secretion of TNF-α and IL-1β. These findings suggest that coptisine might be a potential candidate for psoriasis treatment by improving both disease severity and psychological comorbidities.
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Affiliation(s)
| | | | - Heung-Mook Shin
- Department of Physiology, College of Korean Medicine, Dongguk University, Gyeongju 38066, Korea; (L.T.H.N.); (M.-J.C.)
| | - In-Jun Yang
- Department of Physiology, College of Korean Medicine, Dongguk University, Gyeongju 38066, Korea; (L.T.H.N.); (M.-J.C.)
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Enhanced NAMPT-Mediated NAD Salvage Pathway Contributes to Psoriasis Pathogenesis by Amplifying Epithelial Auto-Inflammatory Circuits. Int J Mol Sci 2021; 22:ijms22136860. [PMID: 34202251 PMCID: PMC8267663 DOI: 10.3390/ijms22136860] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/17/2021] [Accepted: 06/21/2021] [Indexed: 01/06/2023] Open
Abstract
Dysregulated cross-talk between immune cells and epithelial compartments is responsible for the onset and amplification of pathogenic auto-inflammatory circuits occurring in psoriasis. NAMPT-mediated NAD salvage pathway has been recently described as an immunometabolic route having inflammatory function in several disorders, including arthritis and inflammatory bowel diseases. To date, the role of NAD salvage pathway has not been explored in the skin of patients affected by psoriasis. Here, we show that NAD content is enhanced in lesional skin of psoriatic patients and is associated to high NAMPT transcriptional levels. The latter are drastically reduced in psoriatic skin following treatment with the anti-IL-17A biologics secukinumab. We provide evidence that NAMPT-mediated NAD+ metabolism fuels the immune responses executed by resident skin cells in psoriatic skin. In particular, intracellular NAMPT, strongly induced by Th1/Th17-cytokines, acts on keratinocytes by inducing hyper-proliferation and impairing their terminal differentiation. Furthermore, NAMPT-mediated NAD+ boosting synergizes with psoriasis-related cytokines in the upregulation of inflammatory chemokines important for neutrophil and Th1/Th17 cell recruitment. In addition, extracellular NAMPT, abundantly released by keratinocytes and dermal fibroblasts, acts in a paracrine manner on endothelial cells by inducing their proliferation and migration, as well as the expression of ICAM-1 membrane molecule and chemokines important for leukocyte recruitment into inflamed skin. In conclusion, our results showed that NAMPT-mediated NAD salvage pathway contributes to psoriasis pathogenic processes by amplifying epithelial auto-inflammatory responses in psoriasis.
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11
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Zou Q, Si J, Guo Y, Yu J, Shi H. Association between serum visfatin levels and psoriasis and their correlation with disease severity: a meta-analysis. J Int Med Res 2021; 49:3000605211002381. [PMID: 33771065 PMCID: PMC8168054 DOI: 10.1177/03000605211002381] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/11/2023] Open
Abstract
Objective To determine the association between serum visfatin levels and psoriasis and to evaluate the correlation between serum visfatin levels and the severity of psoriasis. Methods The electronic databases PubMed®, Embase® and the Cochrane Library were searched for articles published from inception to 1 May 2020. Data were extracted and then standard mean differences (SMDs) and 95% confidence intervals (CIs) were calculated for pooled estimates. Results A total of 11 studies met the inclusion criteria and were included (448 patients diagnosed with psoriasis and 377 controls). This meta-analysis demonstrated that patients with psoriasis had significantly higher levels of visfatin than the controls (SMD = 0.90, 95% CI 0.52, 1.28). Subgroup analyses showed that differences in serum visfatin levels between the patient group and the control group were associated with ethnicity, Psoriasis Area and Severity Index (PASI) and body mass index. Additionally, a meta-analysis of correlations showed that visfatin levels in patients with psoriasis were positively correlated with PASI (r = 0.51, 95% CI 0.14, 0.75). Conclusions This meta-analysis showed that serum visfatin levels in patients with psoriasis were significantly higher than those in the controls and a positive correlation between serum visfatin levels and psoriasis severity was observed.
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Affiliation(s)
- Qian Zou
- Department of Clinical Medicine, Ningxia Medical University, Ningxia, China
| | - Jiawei Si
- Department of Clinical Medicine, Ningxia Medical University, Ningxia, China
| | - Yatao Guo
- Department of Clinical Medicine, Ningxia Medical University, Ningxia, China
| | - Jiayu Yu
- Department of Clinical Medicine, Ningxia Medical University, Ningxia, China
| | - Huijuan Shi
- Department of Dermatovenereology, General Hospital of Ningxia Medical University, Ningxia, China
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Martínez-Morcillo FJ, Cantón-Sandoval J, Martínez-Menchón T, Corbalán-Vélez R, Mesa-Del-Castillo P, Pérez-Oliva AB, García-Moreno D, Mulero V. Non-canonical roles of NAMPT and PARP in inflammation. DEVELOPMENTAL AND COMPARATIVE IMMUNOLOGY 2021; 115:103881. [PMID: 33038343 DOI: 10.1016/j.dci.2020.103881] [Citation(s) in RCA: 15] [Impact Index Per Article: 3.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 08/29/2020] [Revised: 10/01/2020] [Accepted: 10/01/2020] [Indexed: 06/11/2023]
Abstract
Nicotinamide adenine dinucleotide (NAD+) is the most important hydrogen carrier in cell redox reactions. It is involved in mitochondrial function and metabolism, circadian rhythm, the immune response and inflammation, DNA repair, cell division, protein-protein signaling, chromatin remodeling and epigenetics. Recently, NAD+ has been recognized as the molecule of life, since, by increasing NAD+ levels in old or sick animals, it is possible to improve their health and lengthen their lifespan. In this review, we summarize the contribution of NAD+ metabolism to inflammation, with special emphasis in the major NAD+ biosynthetic enzyme, nicotinamide phosphoribosyl transferase (NAMPT), and the NAD+-consuming enzyme, poly(ADP-ribose) polymerase (PARP). The extracurricular roles of these enzymes, i.e. the proinflammatory role of NAMPT after its release, and the ability of PARP to promote a novel form of cell death, known as parthanatos, upon hyperactivation are revised and discussed in the context of several chronic inflammatory diseases.
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Affiliation(s)
- Francisco J Martínez-Morcillo
- Departmento de Biología Celular e Histología, Facultad de Biología, Universidad de Murcia, Spain; Instituto Murciano de Investigación Biosanitaria (IMIB)-Arrixaca, Murcia, Spain; Centro de Investigación Biomédica en Red de Enfermedades Raras (CIBERER), Spain
| | - Joaquín Cantón-Sandoval
- Departmento de Biología Celular e Histología, Facultad de Biología, Universidad de Murcia, Spain; Instituto Murciano de Investigación Biosanitaria (IMIB)-Arrixaca, Murcia, Spain
| | - Teresa Martínez-Menchón
- Instituto Murciano de Investigación Biosanitaria (IMIB)-Arrixaca, Murcia, Spain; Centro de Investigación Biomédica en Red de Enfermedades Raras (CIBERER), Spain; Servicio de Dermatología, Hospital Clínico Universitario Virgen de la Arrixaca, Murcia, Spain
| | - Raúl Corbalán-Vélez
- Instituto Murciano de Investigación Biosanitaria (IMIB)-Arrixaca, Murcia, Spain; Servicio de Dermatología, Hospital Clínico Universitario Virgen de la Arrixaca, Murcia, Spain
| | - Pablo Mesa-Del-Castillo
- Instituto Murciano de Investigación Biosanitaria (IMIB)-Arrixaca, Murcia, Spain; Servicio de Reumatología, Hospital Clínico Universitario Virgen de la Arrixaca, Murcia, Spain
| | - Ana B Pérez-Oliva
- Departmento de Biología Celular e Histología, Facultad de Biología, Universidad de Murcia, Spain; Instituto Murciano de Investigación Biosanitaria (IMIB)-Arrixaca, Murcia, Spain; Centro de Investigación Biomédica en Red de Enfermedades Raras (CIBERER), Spain.
| | - Diana García-Moreno
- Departmento de Biología Celular e Histología, Facultad de Biología, Universidad de Murcia, Spain; Instituto Murciano de Investigación Biosanitaria (IMIB)-Arrixaca, Murcia, Spain; Centro de Investigación Biomédica en Red de Enfermedades Raras (CIBERER), Spain.
| | - Victoriano Mulero
- Departmento de Biología Celular e Histología, Facultad de Biología, Universidad de Murcia, Spain; Instituto Murciano de Investigación Biosanitaria (IMIB)-Arrixaca, Murcia, Spain; Centro de Investigación Biomédica en Red de Enfermedades Raras (CIBERER), Spain.
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13
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Kovács D, Fazekas F, Oláh A, Törőcsik D. Adipokines in the Skin and in Dermatological Diseases. Int J Mol Sci 2020; 21:ijms21239048. [PMID: 33260746 PMCID: PMC7730960 DOI: 10.3390/ijms21239048] [Citation(s) in RCA: 32] [Impact Index Per Article: 6.4] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/31/2020] [Revised: 11/24/2020] [Accepted: 11/25/2020] [Indexed: 12/12/2022] Open
Abstract
Adipokines are the primary mediators of adipose tissue-induced and regulated systemic inflammatory diseases; however, recent findings revealed that serum levels of various adipokines correlate also with the onset and the severity of dermatological diseases. Importantly, further data confirmed that the skin serves not only as a target for adipokine signaling, but may serve as a source too. In this review, we aim to provide a complex overview on how adipokines may integrate into the (patho) physiological conditions of the skin by introducing the cell types, such as keratinocytes, fibroblasts, and sebocytes, which are known to produce adipokines as well as the signals that target them. Moreover, we discuss data from in vivo and in vitro murine and human studies as well as genetic data on how adipokines may contribute to various aspects of the homeostasis of the skin, e.g., melanogenesis, hair growth, or wound healing, just as to the pathogenesis of dermatological diseases such as psoriasis, atopic dermatitis, acne, rosacea, and melanoma.
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Affiliation(s)
- Dóra Kovács
- Department of Dermatology, Faculty of Medicine, University of Debrecen, Nagyerdei krt. 98., 4032 Debrecen, Hungary; (D.K.); (F.F.)
| | - Fruzsina Fazekas
- Department of Dermatology, Faculty of Medicine, University of Debrecen, Nagyerdei krt. 98., 4032 Debrecen, Hungary; (D.K.); (F.F.)
| | - Attila Oláh
- Department of Physiology, Faculty of Medicine, University of Debrecen, Nagyerdei krt. 98., 4032 Debrecen, Hungary;
| | - Dániel Törőcsik
- Department of Dermatology, Faculty of Medicine, University of Debrecen, Nagyerdei krt. 98., 4032 Debrecen, Hungary; (D.K.); (F.F.)
- Correspondence: ; Tel.: +36-52-255-602
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14
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Kanda N, Hoashi T, Saeki H. Nutrition and Psoriasis. Int J Mol Sci 2020; 21:ijms21155405. [PMID: 32751360 PMCID: PMC7432353 DOI: 10.3390/ijms21155405] [Citation(s) in RCA: 71] [Impact Index Per Article: 14.2] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/14/2020] [Revised: 07/26/2020] [Accepted: 07/27/2020] [Indexed: 12/17/2022] Open
Abstract
Psoriasis is a chronic inflammatory skin disease characterized by accelerated tumor necrosis factor-α/interleukin-23/interleukin-17 axis, hyperproliferation and abnormal differentiation of epidermal keratinocytes. Psoriasis patients are frequently associated with obesity, diabetes, dyslipidemia, cardiovascular diseases, or inflammatory bowel diseases. Psoriasis patients often show unbalanced dietary habits such as higher intake of fat and lower intake of fish or dietary fibers, compared to controls. Such dietary habits might be related to the incidence and severity of psoriasis. Nutrition influences the development and progress of psoriasis and its comorbidities. Saturated fatty acids, simple sugars, red meat, or alcohol exacerbate psoriasis via the activation of nucleotide-binding domain, leucine-rich repeats containing family, pyrin domain-containing-3 inflammasome, tumor necrosis factor-α/interleukin-23/interleukin-17 pathway, reactive oxygen species, prostanoids/leukotrienes, gut dysbiosis or suppression of regulatory T cells, while n-3 polyunsaturated fatty acids, vitamin D, vitamin B12, short chain fatty acids, selenium, genistein, dietary fibers or probiotics ameliorate psoriasis via the suppression of inflammatory pathways above or induction of regulatory T cells. Psoriasis patients are associated with dysbiosis of gut microbiota and the deficiency of vitamin D or selenium. We herein present the update information regarding the stimulatory or regulatory effects of nutrients or food on psoriasis and the possible alleviation of psoriasis by nutritional strategies.
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Affiliation(s)
- Naoko Kanda
- Department of Dermatology, Nippon Medical School, Chiba Hokusoh Hospital, Inzai, Chiba 270-1694, Japan
- Correspondence: ; Tel.: +81-476-991-111; Fax: +81-476-991-909
| | - Toshihiko Hoashi
- Department of Dermatology, Nippon Medical School, Bunkyo-Ku, Tokyo 113-8602, Japan; (T.H.); (H.S.)
| | - Hidehisa Saeki
- Department of Dermatology, Nippon Medical School, Bunkyo-Ku, Tokyo 113-8602, Japan; (T.H.); (H.S.)
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15
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Heo YJ, Choi SE, Lee N, Jeon JY, Han SJ, Kim DJ, Kang Y, Lee KW, Kim HJ. CCL20 induced by visfatin in macrophages via the NF-κB and MKK3/6-p38 signaling pathways contributes to hepatic stellate cell activation. Mol Biol Rep 2020; 47:4285-4293. [PMID: 32418112 PMCID: PMC7295719 DOI: 10.1007/s11033-020-05510-7] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/26/2020] [Accepted: 05/08/2020] [Indexed: 12/16/2022]
Abstract
Chemokines interact with hepatic resident cells during inflammation and fibrosis. CC chemokine ligand (CCL) 20 has been reported to be important in inflammation and fibrosis in the liver. We hypothesized that visfatin, an adipocytokine, could play a role in hepatic fibrosis via CCL20. We investigated the effect of visfatin on CCL20 in THP-1 human promonocytic cells and examined the molecular mechanisms involved. Following treatment of THP-1 cells with visfatin, CCL20 expression and secretion were assessed. We assessed the intracellular signaling molecules IKK/NF-κB, JAK2/STAT3, MAPKs, and MKK3/6 by western blotting. We treated THP-1 cells with visfatin and signaling inhibitors, and examined CCL20 mRNA and protein levels. To investigate the effect of visfatin-induced CCL20 expression in hepatic stellate cells (HSCs), LX-2 cells were co-cultured with the culture supernatant of THP-1 cells with or without anti-CCL20 neutralizing antibodies, and fibrosis markers were examined by RT-PCR and immunoblotting. In THP-1 cells, visfatin increased the CCL20 mRNA and protein levels. visfatin increased the activities of the NF-κB, p38, and MLK3/6 signaling pathways but not those of the JAK2/STAT3 and ERK pathways. Visfatin treatment together with an NF-κB, p38, or MLK3 inhibitor reduced the mRNA and protein levels of CCL20. The visfatin-induced CCL20 increased the expression of fibrosis markers and CCR6 in HSCs. Following neutralization of CCL20, the levels of fibrosis markers and CCR6 were decreased. Visfatin increases the expression of CCL20 via the NF-κB and MKK3/6-p38 signaling pathways in macrophages, and visfatin-induced CCL20 expression promotes the fibrosis markers in HSCs.
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Affiliation(s)
- Yu Jung Heo
- Department of Biomedical Sciences, Graduate School of Ajou University, Suwon, Republic of Korea
| | - Sung-E Choi
- Department of Physiology, Ajou University School of Medicine, Suwon, Republic of Korea
| | - Nami Lee
- Department of Endocrinology and Metabolism, Ajou University School of Medicine, 206, World cup-ro, Yeongtong-gu, Suwon, 16499, Republic of Korea
| | - Ja Young Jeon
- Department of Endocrinology and Metabolism, Ajou University School of Medicine, 206, World cup-ro, Yeongtong-gu, Suwon, 16499, Republic of Korea
| | - Seung Jin Han
- Department of Endocrinology and Metabolism, Ajou University School of Medicine, 206, World cup-ro, Yeongtong-gu, Suwon, 16499, Republic of Korea
| | - Dae Jung Kim
- Department of Endocrinology and Metabolism, Ajou University School of Medicine, 206, World cup-ro, Yeongtong-gu, Suwon, 16499, Republic of Korea
| | - Yup Kang
- Department of Physiology, Ajou University School of Medicine, Suwon, Republic of Korea
| | - Kwan Woo Lee
- Department of Endocrinology and Metabolism, Ajou University School of Medicine, 206, World cup-ro, Yeongtong-gu, Suwon, 16499, Republic of Korea
| | - Hae Jin Kim
- Department of Endocrinology and Metabolism, Ajou University School of Medicine, 206, World cup-ro, Yeongtong-gu, Suwon, 16499, Republic of Korea.
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Abstract
Psoriasis is chronic, immune-mediated, inflammatory disease with a multifactorial etiology that affects the skin tissue and causes the appearance of dry and scaly lesions of anywhere on the body. The study of the pathophysiology of psoriasis reveals a network of immune cells that, together with their cytokines, initiates a chronic inflammatory response. Previously attributed to T helper (Th)1 cytokines, currently the Th17 cytokine family is the major effector in the pathogenesis of psoriatic disease and strongly influences the inflammatory pattern established during the disease activity. In addition, the vast network of cells that orchestrates the pathophysiology makes psoriasis complex to study. Along with this, variations in genes that code the cytokines make psoriasis more clinically heterogeneous and present a challenge for the development of drugs that can be used in the treatment of the patients with this disease. Therefore, it is important to clarify the mechanisms by which the cytokines are involved in the pathophysiology of psoriasis and how this knowledge is translated to the medical practice.
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Affiliation(s)
| | - Edna Maria Vissoci Reiche
- Research Laboratory in Applied Immunology, State University of Londrina, Paraná, Brazil; Department of Pathology, Clinical Analysis and Toxicology, State University of Londrina, Paraná, Brazil
| | - Andréa Name Colado Simão
- Research Laboratory in Applied Immunology, State University of Londrina, Paraná, Brazil; Department of Pathology, Clinical Analysis and Toxicology, State University of Londrina, Paraná, Brazil.
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17
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Potential role of adipose tissue and its hormones in burns and critically III patients. Burns 2020; 46:259-266. [DOI: 10.1016/j.burns.2019.01.012] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/16/2018] [Revised: 12/17/2018] [Accepted: 01/30/2019] [Indexed: 12/26/2022]
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18
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Kong Y, Zhang S, Wu R, Su X, Peng D, Zhao M, Su Y. New insights into different adipokines in linking the pathophysiology of obesity and psoriasis. Lipids Health Dis 2019; 18:171. [PMID: 31521168 PMCID: PMC6745073 DOI: 10.1186/s12944-019-1115-3] [Citation(s) in RCA: 48] [Impact Index Per Article: 8.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/21/2019] [Accepted: 09/02/2019] [Indexed: 12/13/2022] Open
Abstract
Psoriasis is a chronic, systemic, hyper-proliferative immune-mediated inflammatory skin disease. The results of epidemiological investigations have shown that psoriasis affects around 2% of the general population worldwide, and the total number of psoriasis patients is more than 6 million in China. Apart from the skin manifestations, psoriasis has been verified to associate with several metabolic comorbidities, such as insulin resistance, diabetes and obesity. However, the underlying mechanism is still not elucidated. Adipocytes, considered as the active endocrine cells, are dysfunctional in obesity which displays increased synthesis and secretion of adipokines with other modified metabolic properties. Currently, growing evidence has pointed to the central role of adipokines in adipose tissue and the immune system, providing new insights into the effect of adipokines in linking the pathophysiology of obesity and psoriasis. In this review, we summarize the current understanding of the pathological role of adipokines and the potential mechanisms whereby different adipokines link obesity and psoriasis. Furthermore, we also provide evidence which identifies a potential therapeutic target aiming at adipokines for the management of these two diseases.
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Affiliation(s)
- Yi Kong
- Department of Dermatology, Hunan Key Laboratory of Medical Epigenomics, the Second Xiangya Hospital of Central South University, 139 Renmin Middle Road, Changsha, 410011, Hunan, China
| | - Suhan Zhang
- Department of Dermatology, Hunan Key Laboratory of Medical Epigenomics, the Second Xiangya Hospital of Central South University, 139 Renmin Middle Road, Changsha, 410011, Hunan, China
| | - Ruifang Wu
- Department of Dermatology, Hunan Key Laboratory of Medical Epigenomics, the Second Xiangya Hospital of Central South University, 139 Renmin Middle Road, Changsha, 410011, Hunan, China
| | - Xin Su
- Department of Cardiovascular Medicine, the Second Xiangya Hospital of Central South University, Changsha, Hunan, China
| | - Daoquan Peng
- Department of Cardiovascular Medicine, the Second Xiangya Hospital of Central South University, Changsha, Hunan, China
| | - Ming Zhao
- Department of Dermatology, Hunan Key Laboratory of Medical Epigenomics, the Second Xiangya Hospital of Central South University, 139 Renmin Middle Road, Changsha, 410011, Hunan, China.
| | - Yuwen Su
- Department of Dermatology, Hunan Key Laboratory of Medical Epigenomics, the Second Xiangya Hospital of Central South University, 139 Renmin Middle Road, Changsha, 410011, Hunan, China.
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19
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Zeng J, Chen X, Lei K, Wang D, Lin L, Wang Y, Li Y, Liu Y, Zhang L, Zuo D, Sun L. Mannan-binding lectin promotes keratinocyte to produce CXCL1 and enhances neutrophil infiltration at the early stages of psoriasis. Exp Dermatol 2019; 28:1017-1024. [PMID: 31260126 DOI: 10.1111/exd.13995] [Citation(s) in RCA: 9] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/18/2019] [Revised: 06/13/2019] [Accepted: 06/21/2019] [Indexed: 11/28/2022]
Abstract
Psoriasis is a chronic, relapsing inflammatory skin disorder. Numerous experimental evidence and therapeutic evidence have shown that the innate immune response is critical for the pathogenesis and development of psoriasis. Mannan-binding lectin (MBL), a prototypic pattern recognition molecule of the innate immune system, plays an essential role in the host defense against certain infections and also appears to be a major regulator of inflammation. In this study, we investigated the function of MBL on the course of experimental murine imiquimod (IMQ)-induced psoriasis. Our data showed that MBL-deficient (MBL-/- ) mice exhibited attenuated skin damage characterized by greatly decreased erythema compared with wild-type control mice during the early stages of IMQ-induced psoriasis-like skin inflammation. The reduced skin inflammation in MBL-/- mice was associated with the decreased infiltration of neutrophils. Furthermore, we have determined that MBL deficiency limited the chemokine CXCL1 production from skin keratinocytes upon IMQ stimulation, which might be responsible for the impaired skin recruitment of neutrophils. Additionally, we have provided the data that MBL protein promotes the IMQ-induced expression of CXCL1 and activation of MAPK/NF-κB signalling pathway in human keratinocyte HaCaT cells in vitro. In summary, our study revealed an unexpected role of MBL on keratinocyte function in skin, thus offering a new insight into the pathogenic mechanisms of psoriasis.
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Affiliation(s)
- Jiaqi Zeng
- Department of Dermatology, The Fifth Affiliated Hospital, Southern Medical University, Guangzhou, China
| | - Xi Chen
- School of Laboratory Medicine and Biotechnology, Institute of Molecular Immunology, Southern Medical University, Guangzhou, China.,School of Basic Medical Sciences, Department of Immunology, Southern Medical University, Guangzhou, China
| | - Ke Lei
- Department of Dermatology, The Fifth Affiliated Hospital, Southern Medical University, Guangzhou, China.,School of Laboratory Medicine and Biotechnology, Institute of Molecular Immunology, Southern Medical University, Guangzhou, China
| | - Di Wang
- Department of Dermatology, The Fifth Affiliated Hospital, Southern Medical University, Guangzhou, China.,School of Laboratory Medicine and Biotechnology, Institute of Molecular Immunology, Southern Medical University, Guangzhou, China
| | - Lin Lin
- Department of Dermatology, The Fifth Affiliated Hospital, Southern Medical University, Guangzhou, China.,School of Basic Medical Sciences, Department of Immunology, Southern Medical University, Guangzhou, China
| | - Yajie Wang
- Department of Dermatology, The Fifth Affiliated Hospital, Southern Medical University, Guangzhou, China
| | - Yao Li
- Department of Dermatology, The Fifth Affiliated Hospital, Southern Medical University, Guangzhou, China
| | - Yunzhi Liu
- School of Laboratory Medicine and Biotechnology, Institute of Molecular Immunology, Southern Medical University, Guangzhou, China.,School of Basic Medical Sciences, Department of Immunology, Southern Medical University, Guangzhou, China
| | - Liyun Zhang
- School of Basic Medical Sciences, Department of Immunology, Southern Medical University, Guangzhou, China
| | - Daming Zuo
- School of Laboratory Medicine and Biotechnology, Institute of Molecular Immunology, Southern Medical University, Guangzhou, China.,School of Basic Medical Sciences, Department of Immunology, Southern Medical University, Guangzhou, China.,Guangdong Provincial Key Laboratory of Proteomics, Southern Medical University, Guangzhou, China
| | - Ledong Sun
- Department of Dermatology, The Fifth Affiliated Hospital, Southern Medical University, Guangzhou, China
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20
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Yamashita H, Morita T, Ito M, Okazaki S, Koto M, Ichikawa Y, Takayama R, Hoashi T, Saeki H, Kanda N. Dietary habits in Japanese patients with psoriasis and psoriatic arthritis: Low intake of meat in psoriasis and high intake of vitamin A in psoriatic arthritis. J Dermatol 2019; 46:759-769. [DOI: 10.1111/1346-8138.15032] [Citation(s) in RCA: 10] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/17/2019] [Accepted: 07/05/2019] [Indexed: 12/15/2022]
Affiliation(s)
| | - Takashi Morita
- Department of Dermatology Nippon Medical School Chiba Hokusoh Hospital Inzai Japan
| | - Michiko Ito
- Department of Dermatology Nippon Medical School TokyoJapan
| | - Shizuka Okazaki
- Department of Dermatology Nippon Medical School Chiba Hokusoh Hospital Inzai Japan
| | - Mototaka Koto
- Department of Dermatology Nippon Medical School Chiba Hokusoh Hospital Inzai Japan
| | - Yuri Ichikawa
- Department of Dermatology Nippon Medical School Chiba Hokusoh Hospital Inzai Japan
| | - Ryoko Takayama
- Department of Dermatology Nippon Medical School TokyoJapan
| | | | - Hidehisa Saeki
- Department of Dermatology Nippon Medical School TokyoJapan
| | - Naoko Kanda
- Department of Dermatology Nippon Medical School Chiba Hokusoh Hospital Inzai Japan
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21
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Chen G, Gong H, Wang T, Wang J, Han Z, Bai G, Han S, Yang X, Zhou W, Liu T, Xiao J. SOSTDC1 inhibits bone metastasis in non-small cell lung cancer and may serve as a clinical therapeutic target. Int J Mol Med 2018; 42:3424-3436. [PMID: 30320379 PMCID: PMC6202094 DOI: 10.3892/ijmm.2018.3926] [Citation(s) in RCA: 10] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/26/2018] [Accepted: 09/27/2018] [Indexed: 12/22/2022] Open
Abstract
Bone metastasis occurs in ~40% patients with non‑small cell lung cancer (NSCLC), resulting in serious morbidity and mortality. Sclerostin domain‑containing protein 1 (SOSTDC1) has been demonstrated to be associated with the development and progression of multiple types of cancer. However, the role of SOSTDC1 in NSCLC bone metastasis remains unclear. In the present study, it was identified that SOSTDC1 was downregulated in NSCLC bone metastatic lesions compared with that in primary tumors, and low SOSTDC1 expression predicted poor prognosis for patients with NSCLC. Functionally, SOSTDC1 overexpression suppressed NSCLC cell proliferation, migration, invasion and cancer cell‑induced osteoclastogenesis, while SOSTDC1 knockdown produced the opposite effect. In addition, a number of potential downstream target genes of SOSTDC1, which were demonstrated to be associated with tumor progression and bone metastasis, were identified in NSCLC cells by RNA deep sequencing and RT‑qPCR assays. The results from the present study may provide useful insight for an improved understanding of the pathogenesis of NSCLC bone metastasis, and suggest that SOSTDC1 may be a potential prognostic biomarker and therapeutic target for NSCLC bone metastasis.
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Affiliation(s)
- Guanghui Chen
- Orthopedic Oncology Center, Changzheng Hospital, Second Military Medical University, Shanghai 200003
| | - Haiyi Gong
- Orthopedic Oncology Center, Changzheng Hospital, Second Military Medical University, Shanghai 200003
| | - Ting Wang
- Orthopedic Oncology Center, Changzheng Hospital, Second Military Medical University, Shanghai 200003
| | - Jian Wang
- Department of Orthopedics, Pudong New District People’s Hospital, Shanghai 201200
| | - Zhitao Han
- Orthopedic Oncology Center, Changzheng Hospital, Second Military Medical University, Shanghai 200003
- School of Medicine and Life Sciences, Nanjing University of Traditional Chinese Medicine, Nanjing, Jiangsu 210023
| | - Guangjian Bai
- Department of Orthopedics, Affiliated Hospital of Taishan Medical University, Taishan Medical University, Tai’an, Shandong 271016
| | - Shuai Han
- Orthopedic Oncology Center, Changzheng Hospital, Second Military Medical University, Shanghai 200003
| | - Xinghai Yang
- Orthopedic Oncology Center, Changzheng Hospital, Second Military Medical University, Shanghai 200003
| | - Wang Zhou
- Orthopedic Oncology Center, Changzheng Hospital, Second Military Medical University, Shanghai 200003
- School of Clinical Medicine, Tsinghua University, Beijing 102218, P.R. China
| | - Tielong Liu
- Orthopedic Oncology Center, Changzheng Hospital, Second Military Medical University, Shanghai 200003
| | - Jianru Xiao
- Orthopedic Oncology Center, Changzheng Hospital, Second Military Medical University, Shanghai 200003
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22
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Deng H, Li Z, Liu G, Li X, Chen Y, Zhang Y, Sun Y, Fu J. Elevated serum interferon γ-inducible protein-10 in women with polycystic ovary syndrome. Gynecol Endocrinol 2017; 33:363-367. [PMID: 28051885 DOI: 10.1080/09513590.2016.1269740] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/27/2022] Open
Abstract
BACKGROUND Interferon γ-induced protein 10 kDa (IP10/CXCL10) is a chemokine related to endocrine disorders; however, the serum concentrations of IP10 in women with polycystic ovary syndrome (PCOS) have not yet been reported. Therefore, we investigated whether IP10 is increased in PCOS patients and its potential clinical value in PCOS patients. METHODS For this research, the serum IP10, glucose, insulin, high sensitivity C-reactive protein (hs-CRP), follicle-stimulating hormone (FSH), luteinizing hormone (LH) and total testosterone (TT) concentrations were measured in 60 women with PCOS and healthy controls. RESULTS The median IP10 concentration was 45.60 pg/mL [interquartile range (IQR):29.75, 79.69], which was significantly higher than that of the body mass index (BMI)-matched controls (median: 36.46 pg/mL; IQR:28.98, 45.80). In the multivariate linear regression analysis, hs-CRP and the homeostasis model assessment of insulin resistance index (HOMA2-IR) were independent predictors of the IP10 values, while FSH was inversely associated with the IP10.No significant association was observed between the IP10 and BMI, glucose, LH and TT. CONCLUSIONS The serum IP10 concentrations increase in women with PCOS, moreover, IP10 appears to be correlated with the inflammatory and IR statuses of PCOS. IP10 may be a potential biomarker to estimate the disease activity of PCOS.
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Affiliation(s)
- Hongli Deng
- a Department of Clinical Laboratory , Affiliated Liuyang Hospital of University of South China, People's Hospital of Liuyang City , Changsha , Hunan , China
| | - Zhibo Li
- a Department of Clinical Laboratory , Affiliated Liuyang Hospital of University of South China, People's Hospital of Liuyang City , Changsha , Hunan , China
| | - Guang Liu
- a Department of Clinical Laboratory , Affiliated Liuyang Hospital of University of South China, People's Hospital of Liuyang City , Changsha , Hunan , China
| | - Xianhua Li
- a Department of Clinical Laboratory , Affiliated Liuyang Hospital of University of South China, People's Hospital of Liuyang City , Changsha , Hunan , China
| | - Yong Chen
- b Department of Clinical Laboratory , Affiliated Changsha Hospital of University of South China, The First Hospital of Changsha City , Changsha , Hunan , China
| | - Yong Zhang
- c Department of Gastrointestinal Surgery , Affiliated Liuyang Hospital of University of South China, People's Hospital of Liuyang City , Chang sha , Hunan , China
| | - Yifan Sun
- d Department of Clinical Laboratory , Third Affiliated Hospital of Guangxi University of Chinese Medicine , Liuzhou , Guangxi , China , and
| | - Jinjian Fu
- e Department of Clinical Laboratory , Liuzhou Maternity and Child Health Care Hospital , Liuzhou , Guangxi , China
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23
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Yang P, Tan J, Yuan Z, Meng G, Bi L, Liu J. Expression profile of cytokines and chemokines in osteoarthritis patients: Proinflammatory roles for CXCL8 and CXCL11 to chondrocytes. Int Immunopharmacol 2016; 40:16-23. [PMID: 27567247 DOI: 10.1016/j.intimp.2016.08.005] [Citation(s) in RCA: 44] [Impact Index Per Article: 4.9] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/06/2016] [Revised: 07/27/2016] [Accepted: 08/03/2016] [Indexed: 02/03/2023]
Abstract
There are interactions between immune response and destruction of articular cartilage/synovial tissue in osteoarthritis (OA), which leads to chronic inflammation and systemic failure of joints. However, the role of immunological factors in the pathogenesis of OA has not been fully elucidated. In this study, expressions of 47 cytokines and chemokines were tested in the peripheral bloods and synovial fluids from 13 normal controls (NCs) and 31 OA patients. The primary chondrocytes, which were isolated from cartilages of OA patients, were stimulated by recombinant CXCL8 and CXCL11 to analyze the proliferation, cytokine secretion, and signaling pathways. The levels of IL-17A, CXCL8, CXCL9, and CXCL11 were elevated in the serum and synovial fluids of OA patients. Moreover, expressions of CXCL8 and CXCL11 were remarkably increased in the synovial fluids of late stage OA. Stimulation of CXCL8/11 resulted in the reduction of primary chondrocytes proliferation with downregulation of G2-M stage but elevation of S stage and apoptosis cells. The secretions of proinflammatory cytokines and MMPs were also increased upon stimulation. Furthermore, CXCL8/11 stimulation induced the higher expressions of phosphorylated STAT3, NF-kB p50 and JNK, but not p38MAPK or ERK1/2. Our findings suggested that CXCL8 and CXCL11 promoted the apoptosis and suppressed the proliferation of chondrocytes probably via influencing JAK-STAT, NF-kB and JNK MAPK signaling pathway and enhancing the expressions of other proinflammatory cytokines. CXCL8/11 may aggravate the disease progression of OA, and may also be served as new therapeutic targets for treatment of OA.
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Affiliation(s)
- Peng Yang
- Institute of Orthopedic Surgery, Xijing Hospital, Fourth Military Medical University, Xi'an, Shaanxi Province, China; Department of Trauma, Xi'an Sino-German Orthopaedic Hospital, Xi'an, Shaanxi Province, China
| | - Jiali Tan
- Department of Orthodontics, Guanghua School of Stomatology, Hospital of Stomatology, Sun Yat-sen University & Guangdong Provincial Key Laboratory of Stomatology, Guangzhou, Guangdong Province, China.
| | - Zhi Yuan
- Institute of Orthopedic Surgery, Xijing Hospital, Fourth Military Medical University, Xi'an, Shaanxi Province, China
| | - Guolin Meng
- Institute of Orthopedic Surgery, Xijing Hospital, Fourth Military Medical University, Xi'an, Shaanxi Province, China
| | - Long Bi
- Institute of Orthopedic Surgery, Xijing Hospital, Fourth Military Medical University, Xi'an, Shaanxi Province, China
| | - Jian Liu
- Institute of Orthopedic Surgery, Xijing Hospital, Fourth Military Medical University, Xi'an, Shaanxi Province, China.
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Chiricozzi A, Raimondo A, Lembo S, Fausti F, Dini V, Costanzo A, Monfrecola G, Balato N, Ayala F, Romanelli M, Balato A. Crosstalk between skin inflammation and adipose tissue-derived products: pathogenic evidence linking psoriasis to increased adiposity. Expert Rev Clin Immunol 2016; 12:1299-1308. [PMID: 27322922 DOI: 10.1080/1744666x.2016.1201423] [Citation(s) in RCA: 65] [Impact Index Per Article: 7.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/08/2023]
Abstract
INTRODUCTION Psoriasis is a chronic skin disorder associated with several comorbid conditions. In psoriasis pathogenesis, the role of some cytokines, including TNF-α and IL-17, has been elucidated. Beside their pro-inflammatory activity, they may also affect glucose and lipid metabolism, possibly promoting insulin resistance and obesity. On the other hand, adipose tissue, secreting adipokines such as chemerin, visfatin, leptin, and adiponectin, not only regulates glucose and lipid metabolism, and endothelial cell function regulation, but it may contribute to inflammation. Areas covered: This review provides an updated 'state-of-the-art' about the reciprocal contribution of a small subset of conventional cytokines and adipokines involved in chronic inflammatory pathways, upregulated in both psoriasis and increased adiposity. A systematic search was conducted using the PubMed Medline database for primary articles. Expert commentary: Because psoriasis is associated with increased adiposity, it would be important to define the contribution of chronic skin inflammation to the onset of obesity and vice versa. Clarifying the pathogenic mechanism underlying this association, a therapeutic strategy having favorable effects on both psoriasis and increased adiposity could be identified.
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Affiliation(s)
| | - Annunziata Raimondo
- b Department of Clinical Medicine and Surgery, Section of Dermatology , University of Naples Federico II , Naples , Italy
| | - Serena Lembo
- c Department of Medicine and Surgery , University of Salerno , Salerno , Italy
| | - Francesca Fausti
- d Skin Biology Laboratory , University of Rome Tor Vergata , Rome , Italy
| | - Valentina Dini
- a Department of Dermatology , University of Pisa , Pisa , Italy
| | - Antonio Costanzo
- e Dermatology Unit, Department of Neuroscience, Mental Health and Sensory Organs (NESMOS) , Sapienza University of Rome , Rome , Italy
| | - Giuseppe Monfrecola
- b Department of Clinical Medicine and Surgery, Section of Dermatology , University of Naples Federico II , Naples , Italy
| | - Nicola Balato
- b Department of Clinical Medicine and Surgery, Section of Dermatology , University of Naples Federico II , Naples , Italy
| | - Fabio Ayala
- b Department of Clinical Medicine and Surgery, Section of Dermatology , University of Naples Federico II , Naples , Italy
| | - Marco Romanelli
- a Department of Dermatology , University of Pisa , Pisa , Italy
| | - Anna Balato
- f Department of Advanced Biomedical Sciences , University of Naples Federico II , Naples , Italy
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Circulating endothelial cells and serum visfatin are indicators of cardiovascular disease risk in psoriasis patients. DERMATOL SIN 2016. [DOI: 10.1016/j.dsi.2015.07.004] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/23/2022] Open
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Okan G, Baki AM, Yorulmaz E, Doğru-Abbasoğlu S, Vural P. Serum Visfatin, Fetuin-A, and Pentraxin 3 Levels in Patients With Psoriasis and Their Relation to Disease Severity. J Clin Lab Anal 2015; 30:284-9. [PMID: 25867925 DOI: 10.1002/jcla.21850] [Citation(s) in RCA: 17] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/10/2014] [Accepted: 02/24/2015] [Indexed: 12/19/2022] Open
Abstract
BACKGROUND Psoriasis is a chronic immune-mediated inflammatory skin disease associated with increase of some pro-inflammatory mediators. We wanted to investigate whether there is a relationship between psoriasis and visfatin, fetuin-A and pentraxin 3 (PTX3)-pro-inflammatory mediators implicated in the development of insulin resistance (IR), metabolic syndrome, and atherosclerosis. METHODS Visfatin, fetuin-A, and PTX3 concentrations were measured in 45 patients with plaque-type psoriasis and 45 healthy controls using enzyme-linked immunosorbent assay (ELISA). RESULTS Serum levels of visfatin, fetuin-A, and PTX3 in patients with psoriasis were found to be higher than in healthy controls (P = 0.002, P = 0.009, P < 0.001, respectively). Psoriasis area and severity index (PASI) score correlated significantly with visfatin and fetuin-A levels (P = 0.011, P = 0.040, respectively). There was a significant positive correlation between visfatin and fetuin-A (P < 0.001). PTX3 levels were correlated positively with homeostasis model assessment (HOMA-IR), insulin, triglyceride (TG), and very low density lipoprotein cholesterol (VLDL; P = 0.009, P = 0.007, P = 0.023, P = 0.024, respectively). CONCLUSIONS Increased serum visfatin, fetuin-A, and PTX3 levels, and the presence of positive correlation between visfatin, fetuin-A, and PASI score, probably reflect the inflammatory state and IR seen in psoriasis.
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Affiliation(s)
- Gökhan Okan
- Dermatology Department, Kemerburgaz University, Istanbul
| | - Adile Merve Baki
- Istanbul Faculty of Medicine, Department of Biochemistry, Istanbul University, Istanbul
| | - Eda Yorulmaz
- Department of Biochemistry, Medical Park Bahçelievler Hospital, Istanbul
| | - Semra Doğru-Abbasoğlu
- Istanbul Faculty of Medicine, Department of Biochemistry, Istanbul University, Istanbul
| | - Pervin Vural
- Istanbul Faculty of Medicine, Department of Biochemistry, Istanbul University, Istanbul
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Khurram SA, Bingle L, McCabe BM, Farthing PM, Whawell SA. The chemokine receptors CXCR1 and CXCR2 regulate oral cancer cell behaviour. J Oral Pathol Med 2014; 43:667-74. [PMID: 24965032 DOI: 10.1111/jop.12191] [Citation(s) in RCA: 29] [Impact Index Per Article: 2.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 03/06/2014] [Indexed: 01/31/2023]
Abstract
BACKGROUND Chemokines regulate physiological and pathological leucocyte trafficking, and chemokine receptors play a role in tumorigenesis. Expression of interleukin-8 (IL-8) receptors CXCR1 and CXCR2 has been shown in oral squamous cell carcinoma (OSCC) but remains poorly characterised. This aim of this study was to investigate CXCR1 and CXCR2 expression on normal oral keratinocytes (NOKs) and oral cancer cell lines (OCCL) and their relative response when exposed to IL-8 and growth-related oncogene-α (which selectively binds CXCR2). METHODS mRNA and protein expression was studied using RT-PCR, immunocytochemistry and flow cytometry. ELISAs were used to investigate ERK1/2 phosphorylation and MMP production, whereas a MTS-based assay was employed to study proliferation. Migration assays were carried out using modified Boyden chambers with a matrigel coating used for invasion assays. RESULTS mRNA expression of CXCR1 and CXCR2 was seen in both NOKs and OCCL with significantly higher protein expression in OCCL. Exposure to IL-8 and GROα increased intracellular ERK phosphorylation, proliferation, migration and invasion with OCCL showing a greater response than NOKs. These effects were mediated through CXCR1 and CXCR2 (for IL-8) and CXCR2 (for GROα) as receptor-blocking antibodies significantly inhibited the responses. IL-8 and GROα also increased MMP-9 release from NOKs and OCCL with significantly higher amounts released by OCCL. However, an increase in MMP-7 production was only seen in OCCL. CONCLUSIONS Functional CXCR1 and CXCR2 exist on normal and cancerous oral epithelial cells, and our data suggests a role for these receptors in oral cancer biology.
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Affiliation(s)
- Syed A Khurram
- Unit of Oral and Maxillofacial Pathology, School of Clinical Dentistry, University of Sheffield, Sheffield, UK
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Dalamaga M, Papadavid E. Adipocytokines and psoriasis: Insights into mechanisms linking obesity and inflammation to psoriasis. World J Dermatol 2013; 2:27-31. [DOI: 10.5314/wjd.v2.i4.27] [Citation(s) in RCA: 7] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/01/2013] [Revised: 06/26/2013] [Accepted: 07/05/2013] [Indexed: 02/06/2023] Open
Abstract
Psoriasis has been lately seen as a potential systemic inflammatory disease associated with a range of co-morbidities exhibiting an overlapping pathology and presenting a great social health impact such as cardiovascular disease and metabolic diseases, including obesity. Adipose tissue is considered a genuine endocrine organ producing a variety of bioactive adipocytokines, like leptin, adiponectin, resistin and visfatin, participating in physiological and pathological processes, such as energy balance, insulin sensitivity and resistance, immunity, inflammation, hematopoiesis and angiogenesis. Adipocytokines could serve as a missing link in the association between psoriasis, obesity and metabolic co-morbidities. In chronic inflammatory disease states such as psoriasis, adipocytokines may be implicated in psoriasis onset, progression, severity as well as in the pathogenesis of co-morbidities. Measuring serum adipocytokine levels in the future may be useful in predicting psoriasis severity, progression, treatment outcome and risk of any co-morbidities. Interventions to decrease pro-inflammatory adipocytokine levels could offer preventive and therapeutic options for improving psoriasis severity and protecting against its co-morbidities. Candidate strategic interventions incorporate increased physical activity, weight control and pharmacologic approaches such as metformin. However, the mechanisms underlying the actions of adipocytokines in psoriasis as well as their potential diagnostic, prognostic and/or therapeutic utility require further investigation with larger prospective, longitudinal and mechanistic studies.
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Sobolev VV, Nikol’skaya TA, Zolotarenko AD, Piruzyan ES, Bruskin SA. Expression of bioinformatically identified genes in skin of psoriasis patients. RUSS J GENET+ 2013. [DOI: 10.1134/s1022795413100116] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/23/2022]
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Wilson NO, Solomon W, Anderson L, Patrickson J, Pitts S, Bond V, Liu M, Stiles JK. Pharmacologic inhibition of CXCL10 in combination with anti-malarial therapy eliminates mortality associated with murine model of cerebral malaria. PLoS One 2013; 8:e60898. [PMID: 23630573 PMCID: PMC3618178 DOI: 10.1371/journal.pone.0060898] [Citation(s) in RCA: 48] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/14/2012] [Accepted: 03/04/2013] [Indexed: 02/05/2023] Open
Abstract
Despite appropriate anti-malarial treatment, cerebral malaria (CM)-associated mortalities remain as high as 30%. Thus, adjunctive therapies are urgently needed to prevent or reduce such mortalities. Overproduction of CXCL10 in a subset of CM patients has been shown to be tightly associated with fatal human CM. Mice with deleted CXCL10 gene are partially protected against experimental cerebral malaria (ECM) mortality indicating the importance of CXCL10 in the pathogenesis of CM. However, the direct effect of increased CXCL10 production on brain cells is unknown. We assessed apoptotic effects of CXCL10 on human brain microvascular endothelial cells (HBVECs) and neuroglia cells in vitro. We tested the hypothesis that reducing overexpression of CXCL10 with a synthetic drug during CM pathogenesis will increase survival and reduce mortality. We utilized atorvastatin, a widely used synthetic blood cholesterol-lowering drug that specifically targets and reduces plasma CXCL10 levels in humans, to determine the effects of atorvastatin and artemether combination therapy on murine ECM outcome. We assessed effects of atorvastatin treatment on immune determinants of severity, survival, and parasitemia in ECM mice receiving a combination therapy from onset of ECM (day 6 through 9 post-infection) and compared results with controls. The results indicate that CXCL10 induces apoptosis in HBVECs and neuroglia cells in a dose-dependent manner suggesting that increased levels of CXCL10 in CM patients may play a role in vasculopathy, neuropathogenesis, and brain injury during CM pathogenesis. Treatment of ECM in mice with atorvastatin significantly reduced systemic and brain inflammation by reducing the levels of the anti-angiogenic and apoptotic factor (CXCL10) and increasing angiogenic factor (VEGF) production. Treatment with a combination of atorvastatin and artemether improved survival (100%) when compared with artemether monotherapy (70%), p<0.05. Thus, adjunctively reducing CXCL10 levels and inflammation by atorvastatin treatment during anti-malarial therapy may represent a novel approach to treating CM patients.
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Affiliation(s)
- Nana O. Wilson
- Department of Microbiology, Biochemistry, and Immunology, Morehouse School of Medicine, Atlanta, Georgia, United States of America
| | - Wesley Solomon
- Department of Microbiology, Biochemistry, and Immunology, Morehouse School of Medicine, Atlanta, Georgia, United States of America
| | - Leonard Anderson
- Cardiovascular Research Institute, Morehouse School of Medicine, Atlanta, Georgia, United States of America
| | - John Patrickson
- Department of Pathology, Morehouse School of Medicine, Atlanta, Georgia, United States of America
| | - Sidney Pitts
- Department of Pathology, Morehouse School of Medicine, Atlanta, Georgia, United States of America
| | - Vincent Bond
- Department of Microbiology, Biochemistry, and Immunology, Morehouse School of Medicine, Atlanta, Georgia, United States of America
| | - Mingli Liu
- Department of Microbiology, Biochemistry, and Immunology, Morehouse School of Medicine, Atlanta, Georgia, United States of America
| | - Jonathan K. Stiles
- Department of Microbiology, Biochemistry, and Immunology, Morehouse School of Medicine, Atlanta, Georgia, United States of America
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Hau CS, Kanda N, Noda S, Tatsuta A, Kamata M, Shibata S, Asano Y, Sato S, Watanabe S, Tada Y. Visfatin enhances the production of cathelicidin antimicrobial peptide, human β-defensin-2, human β-defensin-3, and S100A7 in human keratinocytes and their orthologs in murine imiquimod-induced psoriatic skin. THE AMERICAN JOURNAL OF PATHOLOGY 2013; 182:1705-17. [PMID: 23499548 DOI: 10.1016/j.ajpath.2013.01.044] [Citation(s) in RCA: 29] [Impact Index Per Article: 2.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Subscribe] [Scholar Register] [Received: 07/07/2012] [Revised: 01/16/2013] [Accepted: 01/17/2013] [Indexed: 12/30/2022]
Abstract
Psoriasis, a chronic inflammatory dermatosis, is frequently associated with metabolic disorders, suggesting that adipokines are involved in its pathogenesis. We recently reported that the adipokine visfatin activates NF-κB and STAT3 in keratinocytes. Antimicrobial peptide expression is enhanced in psoriatic lesions and may promote disease development. Here, we investigated the effects of visfatin on antimicrobial peptide expression. In vitro, visfatin enhanced basal and tumor necrosis factor-α (TNF-α)-induced mRNA expression and secretion of cathelicidin antimicrobial peptide (CAMP), and enhanced TNF-α-induced human β-defensin-2 (hBD-2), hBD-3, and S100A7 mRNA expression and secretion in human keratinocytes. siRNAs targeting CCAAT/enhancer-binding protein-α (C/EBPα) suppressed visfatin-induced and visfatin plus TNF-α-induced CAMP production. siRNAs targeting NF-κB p65 and STAT3 suppressed visfatin plus TNF-α-induced hBD-2 and S100A7 production. siRNAs targeting c-Jun and STAT3 suppressed visfatin plus TNF-α-induced hBD-3 production. Visfatin and/or TNF-α enhanced C/EBP transcriptional activity and C/EBPα phosphorylation, which were suppressed by p38 mitogen-activated protein kinase (MAPK) inhibition. Visfatin and/or TNF-α induced p38 MAPK phosphorylation. Visfatin increased mRNA and protein expression of CAMP, hBD-2, hBD-3, and S100A7 orthologs in murine imiquimod-treated skin, mimicking psoriasis. In conclusion, visfatin enhances CAMP, hBD-2, hBD-3, and S100A7 production in human keratinocytes and their orthologs in murine imiquimod-treated psoriatic skin. Visfatin may potentiate the development of psoriasis via antimicrobial peptides.
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Affiliation(s)
- Carren S Hau
- Department of Dermatology, Teikyo University School of Medicine, Tokyo, Japan
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Evaluation of adipokines: apelin, visfatin, and resistin in children with atopic dermatitis. Mediators Inflamm 2013; 2013:760691. [PMID: 23476106 PMCID: PMC3586507 DOI: 10.1155/2013/760691] [Citation(s) in RCA: 22] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/09/2012] [Revised: 12/27/2012] [Accepted: 12/28/2012] [Indexed: 02/01/2023] Open
Abstract
Very little is known about the role of adipokines in atopic dermatitis (AD) in children. This study aimed at analyzing the serum levels of resistin, apelin, and visfatin in children with AD in relation to body weight, AD severity, and gender. Serum concentration of adipokines was measured in 27 children with AD and in 46 healthy subjects. Selected biochemical parameters were evaluated and skin prick test was performed. Serum levels of resistin and apelin were significantly higher, whereas serum visfatin concentration was significantly lower in children with AD versus healthy controls, although an increase in resistin levels was exclusively demonstrated in boys. In AD group, a significant increase in apelin levels in girls was documented. There was no relationship between adipokines levels and the degree of allergic sensitization. Receiver operating characteristic curve analysis demonstrated that the serum apelin cutoff value differentiating children with AD from those without was >137.8 pg/mL. Resistin and visfatin cutoff values were >3.8 ng/mL and ≤ 2.13 ng/mL, respectively. Apelin and visfatin can serve as excellent indicators to distinguish children with AD from those without disease.
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Nogueira AVB, Nokhbehsaim M, Eick S, Bourauel C, Jäger A, Jepsen S, Cirelli JA, Deschner J. Regulation of visfatin by microbial and biomechanical signals in PDL cells. Clin Oral Investig 2013; 18:171-8. [PMID: 23404558 DOI: 10.1007/s00784-013-0935-1] [Citation(s) in RCA: 50] [Impact Index Per Article: 4.2] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/07/2012] [Accepted: 01/28/2013] [Indexed: 12/30/2022]
Abstract
OBJECTIVES This in vitro study was established to examine whether visfatin thought to be a link between periodontitis and obesity is produced by periodontal ligament (PDL) cells and, if so, whether its synthesis is modulated by microbial and/or biomechanical signals. MATERIALS AND METHODS PDL cells seeded on BioFlex® plates were exposed to the oral pathogen Fusobacterium nucleatum ATCC 25586 and/or subjected to biomechanical strain for up to 3 days. Gene expression of visfatin and toll-like receptors (TLR) 2 and 4 was analyzed by RT-PCR, visfatin protein synthesis by ELISA and immunocytochemistry, and NFκB nuclear translocation by immunofluorescence. RESULTS F. nucleatum upregulated the visfatin expression in a dose- and time-dependent fashion. Preincubation with neutralizing antibodies against TLR2 and TLR4 caused a significant inhibition of the F. nucleatum-upregulated visfatin expression at 1 day. F. nucleatum stimulated the NFκB nuclear translocation. Biomechanical loading reduced the stimulatory effects of F. nucleatum on visfatin expression at 1 and 3 days and also abrogated the F. nucleatum-induced NFκB nuclear translocation at 60 min. Biomechanical loading inhibited significantly the expression of TLR2 and TLR4 at 3 days. The regulatory effects of F. nucleatum and/or biomechanical loading on visfatin expression were also observed at protein level. CONCLUSIONS PDL cells produce visfatin, and this production is enhanced by F. nucleatum. Biomechanical loading seems to be protective against the effects of F. nucleatum on visfatin expression. CLINICAL RELEVANCE Visfatin produced by periodontal tissues could play a major role in the pathogenesis of periodontitis and the interactions with obesity and other systemic diseases.
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Affiliation(s)
- Andressa Vilas Boas Nogueira
- Department of Diagnosis and Surgery, School of Dentistry at Araraquara, Univ Estadual Paulista -- UNESP, Araraquara, Brazil
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Gerdes S, Osadtschy S, Rostami-Yazdi M, Buhles N, Weichenthal M, Mrowietz U. Leptin, adiponectin, visfatin and retinol-binding protein-4 - mediators of comorbidities in patients with psoriasis? Exp Dermatol 2012; 21:43-7. [PMID: 22151390 DOI: 10.1111/j.1600-0625.2011.01402.x] [Citation(s) in RCA: 70] [Impact Index Per Article: 5.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/21/2022]
Abstract
White adipose tissue is known to be involved in numerous physiological processes such as insulin-mediated functions, lipid and glucose metabolism, vascular changes and coagulation. These processes are mainly mediated by adipokines that are secreted either from adipocytes or cells of the stromal-vascular fraction of adipose tissue. In obesity, a shift in the production of adipokines can mediate the development of associated diseases, such as metabolic syndrome, and vascular complications, such as artherosclerosis, myocardial infarction or stroke, which are known comorbidities of psoriasis too. As obesity is a frequently seen comorbidity in psoriasis patients, adipokines could be involved in the pathogenesis of psoriasis and/or its comorbidities either dependently or independently from obesity. Therefore, this study investigates the levels of four major adipokines in psoriasis patients compared with a control group of healthy volunteers without chronic inflammatory diseases in relation to body composition. Leptin, adiponectin (high molecular weight (HMW) and total adiponectin), visfatin and retinol-binding protein 4 (RBP4) have been analysed in 79 psoriasis patients and in 80 healthy volunteers. It was shown that HMW adiponectin (OR 1.3755; P = 0.0094) and visfatin (OR 1.1267; P = 0.0472) are independently increased, and RBP4 (OR 0.9884; P < 0.0001) is independently decreased in psoriasis. In conclusion, increased levels of HMW adiponectin and decreased levels of RBP4 could be a mechanism in a chronic inflammatory state that helps to protect against vascular and metabolic disorders, whereas the increase of the pro-inflammatory adipokine visfatin could lead to atherosclerosis and vascular disorders found in psoriasis.
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Affiliation(s)
- Sascha Gerdes
- Psoriasis-Center at the Department of Dermatology, University Medical Center Schleswig-Holstein, Campus Kiel, Kiel, Germany.
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