Mechanisms of Helicobacter induced modulation of TRAIL death signal transduction(2/2)
Date Issued
2004
Date
2004
Author(s)
許秉寧
DOI
922320B002160
Abstract
Helicobacter pylori (H. pylori) causes a common chronic infection of humans
that causes gastritis and peptic ulcer diseases. The enhanced gastric epithelial cell
apoptosis observed during infection with H. pylori has been suggested to be of
significance in the pathogenesis of gastritis. In addition to direct triggering cell
apoptosis by H. pylori cytotoxins, in our preliminary study, we demonstrated that H.
pylori could modulate intracellular death signal transduction regulatory mechanisms
and confer sensitivity to TNF-related apoptosis inducing ligand (TRAIL) -mediated
apoptosis in gastric epithelial cells. The gastric epithelial cell lines, AGS and KATO
III, which were resistant to TRAIL-induced cell death in vitro; however, when both
AGS and KATO III cells exposed to H. pylori, they exhibited significant apoptosis to
TRAIL. The H. pylori induced enhancement of TRAIL mediated apoptosis in gastric
epithelial cells could be specifically blocked by Caspase-3 and Caspase-8 inhibitors,
indicating that the alteration of TRAIL sensitivity by H. pylori is via modulation of
intracellular TRAIL death signal transduction regulation. Thus, in addition to direct
trigger apoptosis in gastric epithelial cells, H. pylori can induce sensitivity to
TRAIL-mediated apoptosis by altering intracellular signal transduction regulation in
gastric epithelial cells. In this project, we attempt to further investigate the possible
molecular mechanisms of TRAIL induced death signals modulated by Helicobacter as
well as the pathogenesis of gastric mucosa damage induced by H. pylori infection in
an in vitro co-culture system. We were able to demonstrated that the induction of TRAIL sensitivity by H. pylori is dependent on viable bacteria and direct contact with
cells. H. pylori induced sensitivity to TRAIL-mediated apoptosis in gastric epithelial
cells is dependent on activation of caspase-8 downstream pathway to convey the death
signal to mitochondria, leading to activation of mitochondrial pathway and breaking
the apoptosis resistance. This study will elucidate the mechanism of apoptosis signal
transduction modulation after interaction with H. pylori.
Subjects
Helicobacter pylori
TRAIL
apoptosis
human gastric epithelial cells
mitochondria
SDGs
Publisher
臺北市：國立臺灣大學醫學院免疫學研究所
Type
journal article
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