Helicobacter pylori sensitizes TNF-related apoptosisinducing ligand (TRAIL)-mediated apoptosis in human gastric epithelial cells through regulation of FLIP
Journal
Cell Death and Disease
Journal Volume
5
Journal Issue
3
Date Issued
2014
Author(s)
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. ? 2014 Macmillan Publishers Limited All rights reserved.
SDGs
Other Subjects
caspase 8; death domain receptor signaling adaptor protein; FLICE inhibitory protein; tumor necrosis factor related apoptosis inducing ligand; apoptosis; article; controlled study; down regulation; enzyme activation; epithelium cell; Helicobacter infection; Helicobacter pylori; human; human cell; modulation; nonhuman; pathogenesis; priority journal; protein assembly; regulatory mechanism; sensitization; signal transduction; stomach epithelium; stomach injury; Apoptosis; BH3 Interacting Domain Death Agonist Protein; CASP8 and FADD-Like Apoptosis Regulating Protein; Caspase 8; Cell Line, Tumor; Cytochromes c; Death Domain Receptor Signaling Adaptor Proteins; Dose-Response Relationship, Drug; Enzyme Activation; Epithelial Cells; Helicobacter Infections; Helicobacter pylori; Humans; Mitochondria; Recombinant Proteins; Signal Transduction; Stomach; Time Factors; TNF-Related Apoptosis-Inducing Ligand
Publisher
Nature Publishing Group
Type
journal article