H Pylori
Copyright ©The Author(s) 2004. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Gastroenterol. Aug 15, 2004; 10(16): 2334-2339
Published online Aug 15, 2004. doi: 10.3748/wjg.v10.i16.2334
Helicobacter pylori enhances tumor necrosis factor-related apoptosis-inducing ligand-mediated apoptosis in human gastric epithelial cells
Yi-Ying Wu, Hwei-Fang Tsai, We-Cheng Lin, Ai-Hsiang Chou, Hui-Ting Chen, Jyh-Chin Yang, Ping-I Hsu, Ping-Ning Hsu
Yi-Ying Wu, Hwei-Fang Tsai, We-Cheng Lin, Ai-Hsiang Chou, Hui-Ting Chen, Ping-Ning Hsu, Graduate Institute of Immunology, College of Medicine, National Taiwan University, Taiwan, China
Jyh-Chin Yang, Ping-I Hsu, Department of Internal Medicine, National Taiwan University Hospital, Taipei, Taiwan, China
Author contributions: All authors contributed equally to the work.
Supported by the Grants from the National Health Research Institute, Taiwan, NHRI-GI-EX89S942C and the National Science Council, NSC-90-2314B-075B003, NSC 91-2320B-002 and the National Taiwan University Hospital, NTUH 89S2011
Correspondence to: Dr. Ping-Ning Hsu, Graduate Institute of Immunology, College of Medicine, National Taiwan University, No. 1, Sec. 1, Jen-Ai Road, Taipei, Taiwan, China. phsu@ha.mc.ntu.edu.tw
Telephone: +886- 223123456 Fax: +886- 223217921
Received: March 15, 2004
Revised: April 1, 2004
Accepted: April 15, 2004
Published online: August 15, 2004
Abstract

AIM: To investigate the relations between tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) and Helicobacter pylori (H pylori) infection in apoptosis of gastric epithelial cells and to assess the expression of TRAIL on the surface of infiltrating T-cells in H pylori-infected gastric mucosa.

METHODS: Human gastric epithelial cell lines and primary gastric epithelial cells were co-cultured with H pyloriin vitro, then recombinant TRAIL proteins were added to the culture. Apoptosis of gastric epithelial cells was determined by a specific ELISA for cell death. Infiltrating lymphocytes were isolated from H pylori-infected gastric mucosa, and expression of TRAIL in T cells was analyzed by flow cytometry.

RESULTS: The apoptosis of gastric epithelial cell lines and primary human gastric epithelial cells was mildly increased by interaction with either TRAIL or H pylori alone. Interestingly, the apoptotic indices were markedly elevated when gastric epithelial cells were incubated with both TRAIL and H pylori (Control vs TRAIL and H pylori: 0.51 ± 0.06 vs 2.29 ± 0.27, P = 0.018). A soluble TRAIL receptor (DR4-Fc) could specifically block the TRAIL-mediated apoptosis. Further studies demonstrated that infiltrating T-cells in gastric mucosa expressed TRAIL on their surfaces, and the induction of TRAIL sensitivity by H pylori was dependent upon direct cell contact of viable bacteria, but not CagA and VacA of H pylori.

CONCLUSION: H pylori can sensitize human gastric epithelial cells and enhance susceptibility to TRAIL-mediated apoptosis. Modulation of host cell sensitivity to apoptosis by bacterial interaction adds a new dimension to the immunopathogenesis of H pylori infection.

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