Helicobacter pylori sensitizes TNF-related apoptosisinducing ligand (TRAIL)-mediated apoptosis in human gastric epithelial cells through regulation of FLIP

W. C. Lin, H. F. Tsai, H. J. Liao, C. H. Tang, Y. Y. Wu, P. I. Hsu, A. L. Cheng, P. N. Hsu

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16 引文 斯高帕斯(Scopus)

摘要

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.
原文英語
文章編號e1109
期刊Cell Death and Disease
5
發行號3
DOIs
出版狀態已發佈 - 2014

ASJC Scopus subject areas

  • 細胞生物學
  • 免疫學
  • 癌症研究
  • 細胞與分子神經科學

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