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

Research output: Contribution to journalArticle

13 Citations (Scopus)

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.

Original languageEnglish
Article numbere1109
JournalCell Death and Disease
Volume5
Issue number3
DOIs
Publication statusPublished - 2014

Fingerprint

CASP8 and FADD-Like Apoptosis Regulating Protein
Helicobacter pylori
Stomach
Epithelial Cells
Apoptosis
Ligands
Helicobacter Infections
Death Domain Receptor Signaling Adaptor Proteins
Caspase 8
Helicobacter
Death Domain Receptors
Gastritis
Caspases
Peptic Ulcer
Stomach Neoplasms
Down-Regulation

Keywords

  • Apoptosis signaling
  • DISC
  • FLIP
  • Helicobacter pylori
  • TRAIL

ASJC Scopus subject areas

  • Cell Biology
  • Immunology
  • Cancer Research
  • Cellular and Molecular Neuroscience

Cite this

Helicobacter pylori sensitizes TNF-related apoptosisinducing ligand (TRAIL)-mediated apoptosis in human gastric epithelial cells through regulation of FLIP. / Lin, W. C.; Tsai, H. F.; Liao, H. J.; Tang, C. H.; Wu, Y. Y.; Hsu, P. I.; Cheng, A. L.; Hsu, P. N.

In: Cell Death and Disease, Vol. 5, No. 3, e1109, 2014.

Research output: Contribution to journalArticle

Lin, W. C. ; Tsai, H. F. ; Liao, H. J. ; Tang, C. H. ; Wu, Y. Y. ; Hsu, P. I. ; Cheng, A. L. ; Hsu, P. N. / Helicobacter pylori sensitizes TNF-related apoptosisinducing ligand (TRAIL)-mediated apoptosis in human gastric epithelial cells through regulation of FLIP. In: Cell Death and Disease. 2014 ; Vol. 5, No. 3.
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