|
1
|
Yue Y, Lin X, Qiu X, Yang L, Wang R. The Molecular Roles and Clinical Implications of Non-Coding RNAs in Gastric Cancer. Front Cell Dev Biol 2021; 9:802745. [PMID: 34966746 PMCID: PMC8711095 DOI: 10.3389/fcell.2021.802745] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/27/2021] [Accepted: 11/29/2021] [Indexed: 01/19/2023] Open
Abstract
Gastric cancer (GC) is one of the most common malignancies in the world. It is also the fifth most common cancer in China. In recent years, a large number of studies have proved that non-coding RNAs (ncRNAs) can regulate cell proliferation, invasion, metastasis, apoptosis, and angiogenesis. NcRNAs also influence the therapeutic resistance of gastric cancer. NcRNAs mainly consist of miRNAs, lncRNAs and circRNAs. In this paper, we summarized ncRNAs as biomarkers and therapeutic targets for gastric cancer, and also reviewed their role in clinical trials and diagnosis. We sum up different ncRNAs and related moleculars and signaling pathway in gastric cancer, like Bcl-2, PTEN, Wnt signaling. In addition, the potential clinical application of ncRNAs in overcoming chemotherapy and radiotherapy resistance in GC in the future were also focused on.
Collapse
Affiliation(s)
- Yanping Yue
- Department of Medical Oncology, Affiliated Cancer Hospital, Nantong University, Nantong, China
| | - Xinrong Lin
- Department of Medical Oncology, Affiliated Jinling Hospital, Medical School of Nanjing University, Nanjing, China
| | - Xinyue Qiu
- Department of Medical Oncology, Affiliated Cancer Hospital, Nantong University, Nantong, China
| | - Lei Yang
- Department of Medical Oncology, Affiliated Cancer Hospital, Nantong University, Nantong, China
| | - Rui Wang
- Department of Medical Oncology, Affiliated Jinling Hospital, Medical School of Nanjing University, Nanjing, China
| |
Collapse
|
|
2
|
Iwamuro M, Takahashi T, Watanabe N, Okada H. Isolation of lymphocytes from the human gastric mucosa. World J Methodol 2021; 11:199-207. [PMID: 34322369 PMCID: PMC8299908 DOI: 10.5662/wjm.v11.i4.199] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/31/2020] [Revised: 04/09/2021] [Accepted: 07/09/2021] [Indexed: 02/06/2023] Open
Abstract
Flow cytometry is widely used for lymphocyte immunophenotyping in clinical settings. However, few studies have applied it for analyzing lymphocytes of the gastric mucosa. This review offers an overview of methodologies for isolating lymphocytes from the human stomach. Previously reported articles were reviewed, focusing on procedures for isolating human gastric mucosal lymphocytes. Helicobacter pylori-associated peptic diseases and gastric cancer are two major subjects of research in this field. Enzymatic dissociation, mechanical dissociation, or a combination of the two have been used to isolate lymphocytes from the stomach. Intra-epithelial and lamina propria lymphocytes were separately isolated in several studies. We also summarize the history and present trends in analyzing lymphocytes in patients with gastric disease.
Collapse
Affiliation(s)
- Masaya Iwamuro
- Department of Gastroenterology and Hepatology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama 700-8558, Japan
| | - Takahide Takahashi
- Division of Medical Support, Okayama University Hospital, Okayama 700-8558, Japan
| | - Natsuki Watanabe
- Division of Medical Support, Okayama University Hospital, Okayama 700-8558, Japan
| | - Hiroyuki Okada
- Department of Gastroenterology and Hepatology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama 700-8558, Japan
| |
Collapse
|
|
3
|
Sallas ML, Zapparoli D, Dos Santos MP, Pereira JN, Orcini WA, Peruquetti RL, Chen ES, de Arruda Cardoso Smith M, Payão SLM, Rasmussen LT. Dysregulated Expression of Apoptosis-Associated Genes and MicroRNAs and Their Involvement in Gastric Carcinogenesis. J Gastrointest Cancer 2020; 52:625-633. [PMID: 32583363 DOI: 10.1007/s12029-019-00353-3] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/30/2023]
Abstract
PURPOSE Analyze the expression of caspase-9, Smac/DIABLO, XIAP, let-7a, and let-7b in patients with normal gastric tissue, chronic gastritis, and gastric adenocarcinoma. METHODS The expression of caspase-9, Smac/DIABLO, XIAP, let-7a, and let-7b by qRT-PCR was analyzed in 158 samples from 53 patients with normal gastric mucosa, 86 with chronic gastritis, and 19 with gastric cancer. RESULTS The comparison between the gastric cancer and the control group revealed a decreased expression of caspase-9 in gastric cancer tissues; considering the Helicobacter pylor presence, comparable results were revealed. Smac/DIABLO was increased in gastric cancer cells, while XIAP demonstrated no significant difference in the gene expression. The microRNA analysis revealed a decreased expression of let-7a and let-7b in samples positive to H. pylori infection and in gastric cancer group, regardless of the presence of the bacterium. CONCLUSION Our study provided some evidence of low activity of the intrinsic apoptosis pathway, as well as the influence of H. pylori on let-7a and let-7b expression.
Collapse
Affiliation(s)
| | - Diana Zapparoli
- Universidade do Sagrado Coração (USC), Bauru, São Paulo, Brazil
| | | | | | | | | | | | | | | | | |
Collapse
|
|
4
|
Wu YY, Hsieh CT, Chiu YM, Chou SC, Kao JT, Shieh DC, Lee YJ. GSK-3 inhibitors enhance TRAIL-mediated apoptosis in human gastric adenocarcinoma cells. PLoS One 2018; 13:e0208094. [PMID: 30557366 PMCID: PMC6296518 DOI: 10.1371/journal.pone.0208094] [Citation(s) in RCA: 10] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/19/2018] [Accepted: 11/12/2018] [Indexed: 02/06/2023] Open
Abstract
Resistance to tumor necrosis factor-related apoptosis-inducing ligand (TRAIL)-induced apoptosis has been reported in some cancer cells, including AGS human gastric adenocarcinoma cells. Reducing this resistance might shed light on the treatment of human gastric adenocarcinoma. In this study, we examined whether glycogen synthase kinase-3 (GSK-3) inhibitors can restore TRAIL responsiveness in gastric adenocarcinoma cells. The effect of two GSK-3 inhibitors, SB-415286, and LiCl, on apoptosis signaling of TRAIL in human gastric adenocarcinoma cell lines and primary gastric epithelial cells was analyzed. Both inhibitors can sensitize gastric adenocarcinoma cells, but not primary gastric epithelial cells, to TRAIL-induced apoptosis by increasing caspase-8 activity and its downstream signal transmission. Adding p53 siRNA can downregulate GSK-3 inhibitor-related sensitization to TRAIL-induced apoptosis and caspase-3 activity. GSK-3 inhibitors strongly activate the phosphorylation of JNK. Inhibition of JNK leads to earlier and more intense apoptosis, showing that the activation of JNK may provide anti-apoptotic equilibrium of pro-apoptotic cells. Our observations indicate that GSK-3 inhibitors can sentize AGS gastric adenocarcinoma cells to TRAIL-induced apoptosis. Therefore, in certain types of gastric adenocarcinoma, GSK-3 inhibitor might enhance the antitumor activity of TRAIL and mightbe a promising candidate for the treatment of certain types of gastric adenocarcinoma.
Collapse
Affiliation(s)
- Yi-Ying Wu
- Department of Medical Laboratory Science and Biotechnology, China Medical University, Taichung, Taiwan
- Chinese Medicine Research Center, China Medical University, Taichung, Taiwan
- Research Center for Chinese Herbal Medicine, China Medical University, Taichung, Taiwan
| | - Chin-Tung Hsieh
- Department of Pediatrics, Lo-Hsu Medical Foundation Lotung Poh-Ai Hospital, I-Lan, Taiwan
| | - Ying-Ming Chiu
- Department of Nursing, College of Medicine and Nursing, Hungkuang University, Taichung, Taiwan
- Division of Allergy, Immunology & Rheumatology, Changhua Christian Hospital, Changhua, Taiwan
| | - Shen-Chieh Chou
- Department of Biological Science and Technology, School of Medicine, China Medical University, Taichung, Taiwan
| | - Jung-Ta Kao
- Graduate Institute of Clinical Medical Science, China Medical University, Taichung, Taiwan
- Department of Internal Medicine, School of Medicine, China Medical University Hospital and China Medical University, Taichung, Taiwan
| | - Dong-Chen Shieh
- Department of Nursing, College of Medicine and Nursing, Hungkuang University, Taichung, Taiwan
| | - Yi-Ju Lee
- Institute of Biochemistry, Microbiology and Immunology, Chung Shan Medical University, Taichung, Taiwan
| |
Collapse
|
|
5
|
Saberi S, Pournasr B, Farzaneh Z, Esmaeili M, Hosseini ME, Baharvand H, Mohammadi M. A simple and cost-efficient adherent culture platform for human gastric primary cells, as an in vitro model for Helicobacter pylori infection. Helicobacter 2018; 23:e12489. [PMID: 29774633 DOI: 10.1111/hel.12489] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/30/2022]
Abstract
BACKGROUND Most two- dimensional in vitro models for studying host- H. pylori interactions rely on tumor-derived cell lines, which harbor malignant alterations. The recent development of human gastric organoids has overcome this limitation and provides a highly sophisticated, yet costly, short-term model for H. pylori infection, with restricted use in low-budget centers. METHOD Tissue specimens from upper, middle, and lower stomachs of H. pylori-negative volunteers were collectively dispersed and cultured on mouse embryonic fibroblast (MEF) or collagen-coated plates. Gastric primary cells (GPCs) were evaluated by light microscopy, immunostaining, qRT-PCR and ELISA analysis of cellular secretions, before and after H. pylori infection. RESULTS The formation and long-term (up to 1 year) maintenance of GPCs was highly dependent on adherent inactivated MEF cells, cultured in enriched media. These cells were multipassageable and able to undergo stable freezer storage and subsequent revival. The cellular composition of GPCs included the combination of cytokeratin 18 (CK18) and E-cadherin (E-cad)-positive epithelial cells, MUC5AC-positive gastric cells, and leucine-rich repeat containing G protein-coupled receptor 5 (LGR5)-positive progenitor cells. These cells produced significant amounts of gastric pepsinogens I and II. GPCs also allowed for extended (up to 96 hours) H. pylori infection, during which they underwent morphological alterations (cellular vacuolation and elongation) and hyperproduction of gastric pepsinogens and inflammatory cytokines (IL-8 and TNF-α). CONCLUSION We, hereby, present a simple, consistent, and cost-efficient gastric cell culture system, which provides a suitable model for extended in vitro infection of H. pylori. This platform can be employed for a variety of gastric-related research.
Collapse
Affiliation(s)
- Samaneh Saberi
- HPGC Research Group, Department of Medical Biotechnology, Pasteur Institute of Iran, Tehran, Iran
| | - Behshad Pournasr
- Department of Stem Cells and Developmental Biology, Cell Science Research Center, Royan Institute for Stem Cell Biology and Technology, ACECR, Tehran, Iran
| | - Zahra Farzaneh
- Department of Stem Cells and Developmental Biology, Cell Science Research Center, Royan Institute for Stem Cell Biology and Technology, ACECR, Tehran, Iran
| | - Maryam Esmaeili
- HPGC Research Group, Department of Medical Biotechnology, Pasteur Institute of Iran, Tehran, Iran
| | - Mahmoud Eshagh Hosseini
- Gastroenterology Department, Amiralam Hospital, Tehran University of Medical Sciences, Tehran, Iran
| | - Hossein Baharvand
- Department of Stem Cells and Developmental Biology, Cell Science Research Center, Royan Institute for Stem Cell Biology and Technology, ACECR, Tehran, Iran
- Department of Developmental Biology, University of Science and Culture, Tehran, Iran
| | - Marjan Mohammadi
- HPGC Research Group, Department of Medical Biotechnology, Pasteur Institute of Iran, Tehran, Iran
| |
Collapse
|
|
6
|
Ponzoni M, Ferreri AJ. Bacteria associated with marginal zone lymphomas. Best Pract Res Clin Haematol 2017; 30:32-40. [DOI: 10.1016/j.beha.2017.01.001] [Citation(s) in RCA: 17] [Impact Index Per Article: 2.1] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/03/2016] [Accepted: 01/20/2017] [Indexed: 12/17/2022]
|
|
7
|
Tsai HF, Hsu PN. Modulation of tumor necrosis factor-related apoptosis-inducing ligand (TRAIL)-mediated apoptosis by Helicobacter pylori in immune pathogenesis of gastric mucosal damage. JOURNAL OF MICROBIOLOGY, IMMUNOLOGY, AND INFECTION = WEI MIAN YU GAN RAN ZA ZHI 2016; 50:4-9. [PMID: 26947589 DOI: 10.1016/j.jmii.2016.01.002] [Citation(s) in RCA: 14] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 03/01/2015] [Revised: 12/20/2015] [Accepted: 01/17/2016] [Indexed: 12/28/2022]
Abstract
Helicobacter pylori infection is associated with chronic gastritis, peptic ulcer, gastric carcinoma, and gastric mucosa-associated lymphoid tissue lymphomas. Apoptosis induced by microbial infections is implicated in the pathogenesis of H. pylori infection. Enhanced gastric epithelial cell apoptosis during H. pylori infection was suggested to play an important role in the pathogenesis of chronic gastritis and gastric pathology. In addition to directly triggering apoptosis, H. pylori induces sensitivity to tumor necrosis factor-related apoptosis-inducing ligand (TRAIL)-mediated apoptosis in gastric epithelial cells. Human gastric epithelial cells sensitized to H. pylori confer susceptibility to TRAIL-mediated apoptosis via modulation of death-receptor signaling. The induction of TRAIL sensitivity by H. pylori is dependent upon the activation of caspase-8 and its downstream pathway. H. pylori induces caspase-8 activation via enhanced assembly of the TRAIL death-inducing signaling complex through downregulation of cellular FLICE-inhibitory protein. Moreover, H. pylori infection induces infiltration of T lymphocytes and triggers inflammation to augment apoptosis. In H. pylori infection, significant increases in CCR6+ CD3+ T cell infiltration in the gastric mucosa was observed, and the CCR6 ligand, CCL20 chemokine, was selectively expressed in inflamed gastric tissues. These mechanisms initiate chemokine-mediated T lymphocyte trafficking into inflamed epithelium and induce mucosal injury during Helicobacter infection. This article will review recent findings on the interactions of H. pylori with host-epithelial signaling pathways and events involved in the initiation of gastric pathology, including gastric inflammation and mucosal damage.
Collapse
Affiliation(s)
- Hwei-Fang Tsai
- Department of Internal Medicine, Taipei Medical University Shuang Ho Hospital, Taipei, Taiwan; Graduate Institute of Clinical Medicine, College of Medicine, Taipei Medical University, Taipei, Taiwan
| | - Ping-Ning Hsu
- Graduate Institute of Immunology, College of Medicine, National Taiwan University, Taipei, Taiwan; Department of Internal Medicine, National Taiwan University Hospital, Taipei, Taiwan.
| |
Collapse
|
|
8
|
Lin WC, Tsai HF, Liao HJ, Tang CH, Wu YY, Hsu PI, Cheng AL, Hsu PN. Helicobacter pylori sensitizes TNF-related apoptosis-inducing ligand (TRAIL)-mediated apoptosis in human gastric epithelial cells through regulation of FLIP. Cell Death Dis 2014; 5:e1109. [PMID: 24603337 PMCID: PMC3973194 DOI: 10.1038/cddis.2014.81] [Citation(s) in RCA: 20] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/20/2013] [Revised: 01/30/2014] [Accepted: 02/04/2014] [Indexed: 12/11/2022]
Abstract
Helicobacter pylori (H. pylori) infection is associated with chronic gastritis, peptic ulcer and gastric cancer. Apoptosis induced by microbial infections is implicated in the pathogenesis of H. pylori infection. Here we show that human gastric epithelial cells sensitized to H. pylori confer susceptibility to TRAIL-mediated apoptosis via modulation of death receptor signaling. Human gastric epithelial cells are intrinsically resistant to TRAIL-mediated apoptosis. The induction of TRAIL sensitivity by H. pylori is dependent on the activation of caspase-8 and its downstream pathway. H. pylori induces caspase-8 activation via enhanced assembly of the TRAIL death-inducing signaling complex (DISC) through downregulation of cellular FLICE-inhibitory protein (FLIP). Overexpression of FLIP abolished the H. pylori-induced TRAIL sensitivity in human gastric epithelial cells. Our study thus demonstrates that H. pylori induces sensitivity to TRAIL apoptosis by regulation of FLIP and assembly of DISC, which initiates caspase activation, resulting in the breakdown of resistance to apoptosis, and provides insight into the pathogenesis of gastric damage in Helicobacter infection. Modulation of host apoptosis signaling by bacterial interaction adds a new dimension to the pathogenesis of Helicobacter.
Collapse
Affiliation(s)
- W-C Lin
- Graduate Institute of Immunology, College of Medicine, National Taiwan University, Taipei, Taiwan
| | - H-F Tsai
- Department of Internal Medicine, Taipei Medical University Shuang Ho Hospital, Taipei, Taiwan
- Gradute Institute of Clinical Medicine, College of Medicine, Taipei Medical University, Taipei, Taiwan
| | - H-J Liao
- Graduate Institute of Immunology, College of Medicine, National Taiwan University, Taipei, Taiwan
| | - C-H Tang
- Graduate Institute of Immunology, College of Medicine, National Taiwan University, Taipei, Taiwan
| | - Y-Y Wu
- Department of Medical Laboratory Science and Biotechnology, China Medical University and Hospital, Taichung, Taiwan
| | - P-I Hsu
- Department of Internal Medicine, Veterans General Hospital-Kaohsiung, Kaohsiung, Taiwan
| | - A-L Cheng
- Department of Internal Medicine, National Taiwan University Hospital, Taipei, Taiwan
- Department of Oncology, National Taiwan University Hospital, Taipei, Taiwan
| | - P-N Hsu
- Graduate Institute of Immunology, College of Medicine, National Taiwan University, Taipei, Taiwan
- Department of Internal Medicine, National Taiwan University Hospital, Taipei, Taiwan
| |
Collapse
|
|
9
|
Parra-Cid T, Calvino-Fernández M, Benito-Martínez S, Pérez-Gisbert J. Role of Reactive Oxygen Species and Apoptosis in Helicobacter pylori Infection. SYSTEMS BIOLOGY OF FREE RADICALS AND ANTIOXIDANTS 2014:1849-1870. [DOI: 10.1007/978-3-642-30018-9_143] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 01/04/2025]
|
|
10
|
Marginal zone lymphomas and infectious agents. Semin Cancer Biol 2013; 23:431-40. [PMID: 24090976 DOI: 10.1016/j.semcancer.2013.09.004] [Citation(s) in RCA: 66] [Impact Index Per Article: 5.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/24/2013] [Revised: 09/18/2013] [Accepted: 09/19/2013] [Indexed: 12/18/2022]
Abstract
A link with infectious agents, bacteria and viruses in particular, has been reported for many lymphoma entities. Marginal zone lymphomas (extranodal, nodal and splenic forms) are frequently associated with chronic infections, with important clinical, molecular, biological, and therapeutic implications. The well-known correlation between Helicobacter pylori and gastric MALT-lymphoma, the recently reported links between Chlamydophila psittaci and ocular adnexal MALT-lymphoma and Borrelia burgdorferi and cutaneous MALT lymphoma constitute the best studied examples of lymphomagenic activity of bacteria, while the hepatitis C virus represents the most extensively investigated virus associated with marginal zone lymphomas. Biological and clinical features, therapeutic implications and future perspectives of these lymphoma-microbial associations are discussed in this review.
Collapse
|
|
11
|
El-Adawi H, El-Sheekh M, Khalil M, El-Deeb N, Hussein M. Lactic acid bacterial extracts as anti-Helicobacter pylori: a molecular approach. Ir J Med Sci 2013; 182:439-52. [PMID: 23404362 DOI: 10.1007/s11845-013-0909-y] [Citation(s) in RCA: 15] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/15/2012] [Accepted: 01/15/2013] [Indexed: 12/12/2022]
Abstract
BACKGROUND Helicobacter pylori (H. pylori) infection, the main cause of chronic gastritis, increases gastric cancer risk. Antibiotics-based H. pylori eradication treatment is 90% effective. However, it is expensive and causes side effects and antibiotic resistance. Lactic acid bacteria (LAB) could present a low-cost, large-scale alternative solution to prevent or decrease H. pylori colonization. AIM This work aimed to study the inhibitory effects of LAB strains on the growth and pathogenic activity of H. pylori stains. To this end, we have selected the most virulent H. pylori strains (out of 20 mucosal antral biopsies) regarding cellular vacuolization and induction of apoptosis/necrosis. METHOD The selection of H. pylori pathogenic strains (clinically pre-isolated) were based on their impact of VacA activities on Hep-2 cell line, induction of apoptosis and necrosis in Caco-2 cell line. The Inhibitory effect of LAB strains on the invasion was carried out using the Caco-2 and Hela cell lines, where, they were co-cultured with the pathogenic H. pylori in the presence or absence of LAB extracts. The effect of LAB extracts on TNF-α secretion which induced by H. pylori-LPS was carried out by RT-qPCR. RESULTS L. bulgaricus DSMZ 20080, L. acidophilus and L. plantarum (studied previously and reported as high antioxidant candidate strains) showed the highest anti-pylori activities with inhibition ranged from 51.46 to 88.19%, they preventing the adhesion, invasion and DNA fragmentation of cell lines. In addition, they could reduce the TNF-α expression by 62.13%. CONCLUSION LAB extracts could inhibit the bacterial adhesion and invasion, gastric inflammation and DNA fragmentation induced by Helicobacter pylori.
Collapse
Affiliation(s)
- H El-Adawi
- Department of Medical Biotechnology, Genetic Engineering and Biotech Institute, Mubarak City for Scientific Research, Universities and Research District Sector, New Borg El-Arab, P.O.BOX 29134, Alexandria, Egypt.
| | | | | | | | | |
Collapse
|
|
12
|
Wu YY, Lin CW, Cheng KS, Lin C, Wang YM, Lin IT, Chou YH, Hsu PN. Increased programmed death-ligand-1 expression in human gastric epithelial cells in Helicobacter pylori infection. Clin Exp Immunol 2011; 161:551-9. [PMID: 20646001 DOI: 10.1111/j.1365-2249.2010.04217.x] [Citation(s) in RCA: 65] [Impact Index Per Article: 4.6] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/16/2022] Open
Abstract
B7-H1 [programmed death-ligand-1 (PD-L1)] is a B7-family member that binds to programmed death-1 (PD-1). Recently, deficiency of PD-L1 has been demonstrated to result in accelerated gastric epithelial cell damage in gastritis, and PD-L1 is suggested to play a critical role in regulating T cell homeostasis. Here, we aimed to gain more insight into gastric PD-L1 expression, regulation and function during Helicobacter pylori infection. PD-L1 expression in human gastric epithelial cells was analysed using Western blotting, quantitative polymerase chain reaction and fluorescence activated cell sorter analysis. Furthermore, co-culture experiments of human gastric epithelial cells with primary human T cells or Jurkat T cells were conducted. PD-L1 expression in primary human gastric epithelial cells was strongly enhanced by H. pylori infection and activated T cells, and augmented markedly by further stimulation with interferon-γ or tumour necrosis factor-α. Moreover, PD-L1 expression in gastric epithelial cells significantly induced apoptosis of T cells. Our results indicate that a novel bidirectional interaction between human gastric epithelial cells and lymphocytes modulates PD-L1 expression in human gastric epithelial cells, contributing to the unique immunological properties of the stomach.
Collapse
Affiliation(s)
- Y-Y Wu
- Department of Medical Laboratory Science and Biotechnology, China Medical University and Hospital, Taichung, Taiwan
| | | | | | | | | | | | | | | |
Collapse
|
|
13
|
Lin WC, Tsai HF, Kuo SH, Wu MS, Lin CW, Hsu PI, Cheng AL, Hsu PN. Translocation of Helicobacter pylori CagA into Human B lymphocytes, the origin of mucosa-associated lymphoid tissue lymphoma. Cancer Res 2010; 70:5740-5748. [PMID: 20587516 DOI: 10.1158/0008-5472.can-09-4690] [Citation(s) in RCA: 67] [Impact Index Per Article: 4.5] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/06/2023]
Abstract
Infection by cagA-positive Helicobacter pylori (H. pylori) is strongly associated with gastric carcinomas and gastric mucosa-associated lymphoid tissue (MALT) lymphomas. H. pylori translocates the bacterial protein CagA into gastric epithelial cells, and the translocated CagA deregulates intracellular signaling pathways and thereby initiates pathogenesis. This in turn raised the possibility that H. pylori is associated with the development of MALT lymphomas during persistent infection by direct interaction with B lymphocytes. In this work, we showed that CagA can be directly translocated into human B lymphoid cells by H. pylori, and the translocated CagA undergoes tyrosine phosphorylation and binds to intracellular SH-2. Meanwhile, the translocated CagA induces activation of extracellular signal-regulated kinase and p38 mitogen-activated protein kinase in human B lymphoid cells, and upregulates the expressions of Bcl-2 and Bcl-X(L), which prevents apoptosis. These results provide the first direct evidence for the role of CagA as a bacterium-derived oncoprotein that acts in human B cells, and further implies that CagA is directly delivered into B cells by H. pylori and is associated with the development of MALT lymphomas.
Collapse
MESH Headings
- Antigens, Bacterial/metabolism
- B-Lymphocytes/immunology
- B-Lymphocytes/metabolism
- B-Lymphocytes/pathology
- Bacterial Proteins/metabolism
- Cell Line, Tumor
- Enzyme Activation
- Helicobacter Infections/immunology
- Helicobacter Infections/metabolism
- Helicobacter Infections/pathology
- Helicobacter pylori/metabolism
- Humans
- Immunohistochemistry
- Lymphoma, B-Cell/metabolism
- Lymphoma, B-Cell/microbiology
- Lymphoma, B-Cell/pathology
- Lymphoma, B-Cell, Marginal Zone/immunology
- Lymphoma, B-Cell, Marginal Zone/metabolism
- Lymphoma, B-Cell, Marginal Zone/microbiology
- Mitogen-Activated Protein Kinases/metabolism
- Proto-Oncogene Proteins c-bcl-2/metabolism
- Up-Regulation
- bcl-X Protein/metabolism
Collapse
Affiliation(s)
- Wei-Cheng Lin
- Graduate Institute of Immunology, College of Medicine, National Taiwan University, Taipei, Taiwan
| | | | | | | | | | | | | | | |
Collapse
|
|
14
|
Interplay between Helicobacter pylori and immune cells in immune pathogenesis of gastric inflammation and mucosal pathology. Cell Mol Immunol 2010; 7:255-9. [PMID: 20190789 DOI: 10.1038/cmi.2010.2] [Citation(s) in RCA: 44] [Impact Index Per Article: 2.9] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/14/2022] Open
Abstract
Helicobacter pylori infection is associated with an inflammatory response in the gastric mucosa, leading to chronic gastritis, peptic ulcers, gastric carcinoma and gastric mucosa-associated lymphoid tissue (MALT) lymphomas. Recent studies have shown that apoptosis of gastric epithelial cells is increased during H. pylori infection. Apoptosis induced by microbial infections are factors implicated in the pathogenesis of H. pylori infection. The enhanced gastric epithelial cell apoptosis in H. pylori infection has been suggested to play an important role in the pathogenesis of chronic gastritis and gastric pathology. In addition to directly triggering apoptosis, H. pylori induces sensitivity to tumor-necrosis factor (TNF)-related apoptosis-inducing ligand (TRAIL)-mediated apoptosis in gastric epithelial cells via modulation of TRAIL apoptosis signaling. Moreover, H. pylori infection induces infiltration of T lymphocytes and triggers inflammation to augment apoptosis. In H. pylori infection, there was significantly increased CCR6(+)CD3(+ )T-cell infiltration in the gastric mucosa, and the CCR6 ligand, CCL20 chemokine, was selectively expressed in inflamed gastric tissues. These results implicate that the interaction between CCL20 and CCR6 may play a role in recruiting T cells to the sites of inflammation in the gastric mucosa during Helicobacter infection. Through these mechanisms, chemokine-mediated T lymphocyte trafficking into inflamed epithelium is initiated and the mucosal injury in Helicobacter infection is induced. This article will review the recent novel findings on the interactions of H. pylori with diverse host epithelial signaling pathways and events involved in the initiation of gastric pathology, including gastric inflammation, mucosal damage and development of MALT lymphomas.
Collapse
|
|
15
|
Ferreri AJM, Ernberg I, Copie-Bergman C. Infectious agents and lymphoma development: molecular and clinical aspects. J Intern Med 2009; 265:421-38. [PMID: 19298458 DOI: 10.1111/j.1365-2796.2009.02083.x] [Citation(s) in RCA: 71] [Impact Index Per Article: 4.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/29/2022]
Abstract
This review is focused on the role of infectious agents in the development of some lymphoma entities. Associations involving bacterial infections mostly regard marginal zone B-cell lymphomas of mucosa-associated lymphoid tissue (MALT)-type. Some paradigmatic examples of these associations include the Helicobacter pylori-related gastric MALT lymphoma and the more recently reported links between Chlamydophila psittaci and ocular adnexal MALT lymphomas and Borrelia burgdorferi and cutaneous MALT lymphomas. The well-documented association between Epstein-Barr virus infection and related lymphoproliferative disorders are analysed as an example of lymphotropic virus with tumourigenic activity. Molecular, biological and clinical features as well as therapeutic implications of these associations are analysed and future perspectives in this field are discussed.
Collapse
Affiliation(s)
- A J M Ferreri
- Unit of Lymphoid Malignancies, Medical Oncology Unit, Department of Oncology, San Raffaele Scientific Institute, Milan, Italy.
| | | | | |
Collapse
|
|
16
|
Wu YY, Tsai HF, Lin WC, Hsu PI, Shun CT, Wu MS, Hsu PN. Upregulation of CCL20 and recruitment of CCR6+ gastric infiltrating lymphocytes in Helicobacter pylori gastritis. Infect Immun 2007; 75:4357-4363. [PMID: 17562763 PMCID: PMC1951156 DOI: 10.1128/iai.01660-06] [Citation(s) in RCA: 47] [Impact Index Per Article: 2.6] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/17/2006] [Revised: 12/27/2006] [Accepted: 06/04/2007] [Indexed: 12/26/2022] Open
Abstract
Helicobacter pylori infection is associated with an inflammatory response in the gastric mucosa, leading to chronic gastritis, peptic ulcers, and gastric cancer. There is increased T-cell infiltration at the site of infection with H. pylori. CCR6, a specific beta-chemokine receptor for CCL20 (MIP-3alpha/LARC/exodus), has recently been reported to mediate lymphocyte homeostasis and immune responses in mucosal tissue, and it may play a role in chemokine-mediated lymphocyte trafficking during gastric inflammation. In this study, we investigated the role of CCR6 and its ligand, CCL20, in inducing an inflammatory response in the gastric mucosa during H. pylori infection. Gastric infiltrating T lymphocytes were isolated from endoscopic biopsy specimens of H. pylori gastritis patients and analyzed for the expression of the CCR6 chemokine receptor. Our results demonstrated that there was significantly increased CCR6 expression in CD3(+) T cells infiltrating the gastric mucosa, and the CCR6 ligand, the CCL20 chemokine, was selectively expressed in inflamed gastric tissues. The production of CCL20 was upregulated in response to H. pylori in gastric epithelial cells when there was stimulation by the proinflammatory cytokines interleukin-1beta and tumor necrosis factor alpha. Furthermore, recombinant CCL20 induced lymphocyte chemotaxis migration in fresh gastric T cells ex vivo, indicating that the gastric T cells could migrate toward inflammatory sites via CCR6/CCL20 interaction. Our results suggest that the interaction between CCL20 and CCR6 may play a role in chemokine-mediated lymphocyte trafficking during gastric inflammation in Helicobacter infection.
Collapse
MESH Headings
- Cells, Cultured
- Chemokine CCL20
- Chemokines, CC/biosynthesis
- Chemokines, CC/genetics
- Chemotaxis, Leukocyte/genetics
- Chemotaxis, Leukocyte/immunology
- Chronic Disease
- Gastritis/immunology
- Gastritis/microbiology
- Gastritis/pathology
- Helicobacter Infections/immunology
- Helicobacter Infections/microbiology
- Helicobacter Infections/pathology
- Helicobacter pylori/immunology
- Humans
- Immunologic Memory/genetics
- Inflammation Mediators/metabolism
- Inflammation Mediators/physiology
- Lymphocyte Activation/genetics
- Lymphocyte Activation/immunology
- Macrophage Inflammatory Proteins/biosynthesis
- Macrophage Inflammatory Proteins/genetics
- Receptors, CCR5/biosynthesis
- Receptors, CCR5/genetics
- Receptors, CCR6
- Receptors, CXCR3
- Receptors, Chemokine/biosynthesis
- Receptors, Chemokine/genetics
- T-Lymphocyte Subsets/immunology
- T-Lymphocyte Subsets/metabolism
- T-Lymphocyte Subsets/pathology
- Th1 Cells/immunology
- Th1 Cells/metabolism
- Th1 Cells/pathology
- Up-Regulation/immunology
Collapse
Affiliation(s)
- Yi-Ying Wu
- Graduate Institute of Immunology, College of Medicine, National Taiwan University, 1 Jen-Ai Rd., Sec. 1, Taipei 100, Taiwan
| | | | | | | | | | | | | |
Collapse
|
|
17
|
Krueger S, Hundertmark T, Kuester D, Kalinski T, Peitz U, Roessner A. Helicobacter pylori alters the distribution of ZO-1 and p120ctn in primary human gastric epithelial cells. Pathol Res Pract 2007; 203:433-44. [PMID: 17509776 DOI: 10.1016/j.prp.2007.04.003] [Citation(s) in RCA: 46] [Impact Index Per Article: 2.6] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/11/2007] [Accepted: 04/19/2007] [Indexed: 02/08/2023]
Abstract
Helicobacter pylori infection is related to the development of diverse gastric pathologies, possibly by affecting epithelial junctional complexes that define cell polarity and play an essential role in transepithelial transport and cell-cell adhesion. Using primary gastric epithelial cell cultures, effects of H. pylori on the expression and localization of tight/adherence junction proteins and the resulting morphological changes and migratory capabilities were studied under in vivo-like conditions. Gastric epithelial cells were isolated from biopsies or gastrectomies and maintained in Quantum286 on collagen I-coated culture dishes or cover-slips. Cell cultures were characterized and further analyzed by western blot and immunofluorescent staining for ZO-1, p120ctn, and H. pylori CagA. Morphological changes and migratory response were monitored by time-lapse digital image microscopy. ZO-1 and p120ctn protein expression levels remain unaffected by H. pylori infection. Immunocytochemistry on H. pylori-infected primary cell monolayers focally showed disruption of intercellular ZO-1 staining and accumulation of ZO-1 in small vesicles. H. pylori infection recruited non-phosphorylated p120ctn to perinuclear vesicles. The fraction of phosphorylated p120ctn increased and could be detected in the nucleus, at the cell membrane, and at the leading edge of migrating cells. These alterations, triggered by H. pylori infection, are associated with an elongation phenotype and increased migration.
Collapse
Affiliation(s)
- Sabine Krueger
- Department of Pathology, Otto-von-Guericke University, Leipziger Str. 44, D-39120 Magdeburg, Germany.
| | | | | | | | | | | |
Collapse
|
|
18
|
Zhou C, Ma HS. Effects of lactobacillus on phosphorylated p38 mitogen-activated protein kinase and apoptosis in SGC-7901 cells treated with lipopolysaccharide of Helicobacter pylori. Shijie Huaren Xiaohua Zazhi 2007; 15:807-812. [DOI: 10.11569/wcjd.v15.i8.807] [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] [Indexed: 02/06/2023] Open
Abstract
AIM: To investigate effects of lactobacillus bulgaricus (LBG) on the levels of phosphorylated p38 mitogen-activated protein kinase (P-p38MAPK) and apoptosis index (AI) in gastric cancer cell line SGC-7901 treated with lipopolysaccharide of H. pylori Sydney strain 1 (H. pylori SS1-LPS).
METHODS: Human gastric cancer cell line SGC-7901 was treated with H. pylori SS1-LPS at the concentration of 2.5×103, 2.5×104, 2.5 ×105 EU/L, respectively, after pretreatment for 1 h with 10 mmol/L SB203580 (blocker of p38MAPK) or 1×1013 CFU/L LBG. The level of P-p38MAPK was analyzed by immunocytochemistry after 2 h of H. pylori SS1-LPS treatment. The cell activity was detected by MTT assay after 4、5 and 6 h of treatment, and the apoptosis was measured by flow cytometry at the 6th hour.
RESULTS: H. pylori SS1-LPS inhibited cell activity (0.164 ± 0.028 vs 0.622 ± 0.068, P < 0.05) and up-regulated the level of P-p38MAPK (79.771 ± 1.424 vs 4.075 ± 0.135, P < 0.01) and AI value (10.000% ± 0.510% vs 4.175% ± 0.206%, P < 0.05) in a dose-dependent manner. The level of P-p38MAPK and AI value in SGC-7901 cells were not significantly different between LBG pretreatment group and the controls, and the cell activity and AI value were not markedly different between SB203580 pretreatment group and the controls.
CONCLUSION: H. pylori SS1-LPS may induce the apoptosis of SGC-7901 cells by activating the phosphorylation of p38MAPK, while LBG can prevent H. pylori SS1-LPS-induced apoptosis of SGC-7901 cells by inhibiting the phosphorylation of p38MAPK.
Collapse
|
|
19
|
Ganten TM, Aravena E, Sykora J, Koschny R, Mohr J, Rudi J, Stremmel W, Walczak H. Helicobacter pylori-induced apoptosis in T cells is mediated by the mitochondrial pathway independent of death receptors. Eur J Clin Invest 2007; 37:117-25. [PMID: 17217377 DOI: 10.1111/j.1365-2362.2007.01761.x] [Citation(s) in RCA: 15] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/15/2022]
Abstract
BACKGROUND Chronic infection with Helicobacter pylori is related to the pathogenesis of the noncardia carcinoma of the stomach. In this study we investigated the mechanisms of H. pylori-induced apoptosis in T lymphocytes, which could explain a mechanism of immune evasion facilitating chronic inflammation of the mucosa and gastric carcinogenesis. MATERIALS AND METHODS The supernatant of H. pylori culture was used to study the mechanism of apoptosis induction in human leukaemia T cell lines Jurkat and CEM and in primary T cells. The cytotoxin associated gene A (CagA) and vacuolating cytotoxin A (Vac A) positive bacterial strain H. pylori 60190 (CagA(+), VacA(+)) and as a control the less toxic H. pylori strain Tx30a (CagA(-), VacA(-)) were used to produce the supernatant. Cell death was determined by DNA fragmentation and protein expression by Western blot. RESULTS H. pylori 60190-induced apoptosis was neither blocked by inhibition of the death ligands TRAIL (TNF-related apoptosis-inducing ligand), CD95L/FasL and TNF-alpha (tumour necrosis factor-a) in wild type Jurkat cells nor in FADD(def) (Fas-associated death domain protein) and caspase-8(def) subclones of the Jurkat cell line. Yet, the pancaspase inhibitor zVAD-fmk could inhibit up to 90% of H. pylori-induced apoptosis. Stable transfection of Jurkat wild type cells with Bcl-x(L and) Bcl-2 resulted in marked reduction of H. pylori-induced apoptosis, showing that the mitochondrial pathway is the key regulator. This is supported by the finding that surviving primary human lymphocytes upregulate Bcl-2 when exposed to H. pylori supernatant. CONCLUSIONS H. pylori-induced apoptosis of T cells is mediated by the mitochondrial pathway and could create a local environment that facilitates life-long infection by immune evasion.
Collapse
|
|
20
|
Lehours P, Dupouy S, Chaineux J, Ruskoné-Fourmestraux A, Delchier JC, Morgner A, Mégraud F, Ménard A. Genetic diversity of the HpyC1I restriction modification system in Helicobacter pylori. Res Microbiol 2007; 158:265-71. [PMID: 17346936 DOI: 10.1016/j.resmic.2006.12.002] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/11/2006] [Revised: 12/05/2006] [Accepted: 12/11/2006] [Indexed: 11/30/2022]
Abstract
Helicobacter pylori is unique because of the unusually high number and diversity of its restriction modification (R-M) systems. HpyC1I R-M was recently characterized and contains an endonuclease which is an isoschizomer of the endonuclease BccI. This R-M is involved in adherence to gastric epithelial cells, a crucial step in bacterial pathogenesis. This observation illustrates the fact that R-M systems have other putative biological functions in addition to protecting the bacterial genome from external DNA. The genomic diversity of HpyC1I R-M was evaluated more precisely on a large collection of H. pylori strains by PCR, susceptibility to BccI digestion and sequencing. The results obtained support the mechanism of gain and loss of this R-M system in the H. pylori genome, and suggest that it is an ancestral system which gradually disappears during H. pylori evolution, following successive steps: (1) inactivation of the endonuclease gene, followed or accompanied by: (2) inactivation of the methyltransferase genes, and then: (3) definitive loss, leaving only short endonuclease remnant sequences.
Collapse
|
|
21
|
Kountouras J, Gavalas E, Zavos C, Stergiopoulos C, Chatzopoulos D, Kapetanakis N, Gisakis D. Alzheimer's disease and Helicobacter pylori infection: Defective immune regulation and apoptosis as proposed common links. Med Hypotheses 2006; 68:378-88. [PMID: 16979298 DOI: 10.1016/j.mehy.2006.06.052] [Citation(s) in RCA: 57] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/16/2006] [Accepted: 06/21/2006] [Indexed: 11/20/2022]
Abstract
Although degenerative diseases of the central nervous system, including Alzheimer's disease (AD), have an increasingly high impact on aged population their association with Helicobacter pylori (H. pylori) infection has not as yet been thoroughly researched. Current H. pylori infection appears to induce irregular humoral and cellular immune responses that, owing to the sharing of homologous epitopes (molecular mimicry), cross-react with components of nerves, thereby contributing and possibly perpetuating the apoptotic neural tissue damage observed in neurodegenerative diseases including AD. An association between AD and H. pylori infection has been recently addressed by two studies. A higher seropositivity for anti-H. pylori immunoglobulin G antibodies in 30 patients with AD than in 30 age-matched controls was reported in one study; this serological test, however, has limitations because it does not discriminate between current and old infections. In the other study, by introducing the histological method (the actual gold standard) for diagnosis of H. pylori infection, we reported a higher prevalence of H. pylori infection in 50 AD patients than in 30 anemic controls. This pathogen may influence the pathophysiology of AD by promoting platelet and platelet-leukocyte aggregation; releasing various pro-inflammatory and vasoactive substances; developing cross-mimicry with host antigens; producing reactive oxygen metabolites and circulating lipid peroxides; influencing the apoptotic process; and increasing, through induction of atrophic gastritis, homocysteine, which contributes to vascular disorders implicated in endothelial damage and neurodegeneration.
Collapse
Affiliation(s)
- Jannis Kountouras
- Department of Medicine, Second Medical Clinic, Aristotle University of Thessaloniki, Ippokration Hospital, Thessaloniki, Greece.
| | | | | | | | | | | | | |
Collapse
|
|
22
|
Tsuji S, Tsujii M, Murata H, Nishida T, Komori M, Yasumaru M, Ishii S, Sasayama Y, Kawano S, Hayashi N. Helicobacter pylori eradication to prevent gastric cancer: underlying molecular and cellular mechanisms. World J Gastroenterol 2006; 12:1671-1680. [PMID: 16586533 PMCID: PMC4124339 DOI: 10.3748/wjg.v12.i11.1671] [Citation(s) in RCA: 22] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/13/2005] [Revised: 09/25/2005] [Accepted: 11/10/2005] [Indexed: 02/06/2023] Open
Abstract
Numerous cellular and molecular events have been described in development of gastric cancer. In this article, we overviewed roles of Helicobacter pylori (H pylori) infection on some of the important events in gastric carcinogenesis and discussed whether these cellular and molecular events are reversible after cure of the infection. There are several bacterial components affecting gastric epithelial kinetics and promotion of gastric carcinogenesis. The bacterium also increases risks of genetic instability and mutations due to NO and other reactive oxygen species. Epigenetic silencing of tumor suppressor genes such as RUNX3 may alter the frequency of phenotype change of gastric glands to those with intestinal metaplasia. Host factors such as increased expression of growth factors, cytokines and COX-2 have been also reported in non-cancerous tissue in H pylori-positive subjects. It is noteworthy that most of the above phenomena are reversed after the cure of the infection. However, some of them including overexpression of COX-2 continue to exist and may increase risks for carcinogenesis in metaplastic or dysplastic mucosa even after successful H pylori eradication. Thus, H pylori eradication may not completely abolish the risk for gastric carcinogenesis. Efficiency of the cure of the infection in suppressing gastric cancer depends on the timing and the target population, and warrant further investigation.
Collapse
Affiliation(s)
- Shingo Tsuji
- Department of Gastroenterology and Hepatology, Osaka University Graduate School of Medicine (K1), 2-2 Yamadaoka, Suita, 565-0871 Japan.
| | | | | | | | | | | | | | | | | | | |
Collapse
|
|
23
|
Jiang HX, Nie HM, Deng DH, Qin SY, Tao L, Huang ZN. Helicobacter pylori induces apoptosis of rat gastric epithelial cells in vitro. Shijie Huaren Xiaohua Zazhi 2005; 13:2838-2841. [DOI: 10.11569/wcjd.v13.i24.2838] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/06/2023] Open
Abstract
AIM: To investigate the effect of Helicobacter pylori (H. pylori) sonicated extract on the apoptosis of rat gastric epithelial cells as well as the expression of apoptosis-related genes in vitro.
METHODS: H. pylori sonicated extract from strain Sydney SS-1 was cultured with OUMS-37, a kind of immortalized rat gastric cell lines. Apoptosis of the cells was confirmed according to specific changes of morphology and DNA ladder 24-48 h after co-incubation. The expression of P53 protein was detected by Western blotting and the expression of bax and bcl-2 mRNA were observed by Northern blotting.
RESULTS: The specific morphology of the cells such as shrinkage, condensation, margination of nuclear chromatin and apoptotic bodies were observed under light microscope. DNA ladder was manifested by fragment analysis. Western blotting showed a dose-dependent increased expression of wild-type P53 protein and Northern blotting showed a dose-pendent increased expression of bax mRNA and reduced expression of bcl-2 mRNA in the treated cells.
CONCLUSION: H. pylori sonicated extract induces the apoptosis in vitro through up-regulation of wild-type P53 protein and bax mRNA expression, and down-regulation of bcl-2 mRNA expression, suggesting that H. pylori infection may interrupt the balance between proliferation and apoptosis of the gastric epithelial cells, which plays a key role in gastric carcinogenesis.
Collapse
|