| Summary: | 碩士 === 國立臺灣大學 === 免疫學研究所 === 91 === Helicobacter pylori infection induces inflammatory responses and augments apoptosis in gastric epithelium. Increased apoptosis is associated with inflammation and is critical for pathogenesis of Helicobacter gastritis. In order to investigate role of TRAIL-mediated apoptosis in gastric epithelial cell during H. pylori infection, we used an in vitro co-culture system to study the gastric epithelial cell apoptosis after interaction with H. pylori. Our results demonstrated that H. pylori sensitized human gastric epithelial cells, confer susceptibility to TRAIL mediated apoptosis. This phenomenon was observed in both ATCC standard H. pylori strain and domestic clinical isolate, NTUH-C1. We also showed that the enhanced sensitivity to TRAIL by H. pylori is dependent on viable bacteria. Neither heat-killed nor paraformaldehyde-fixed H. pylori was able to induce TRAIL sensitivity in gastric epithelial cells. Therefore, the enhanced TRAIL sensitivity by H. pylori is via altering intracellular signaling pathway to confer susceptibility to TRAIL induced apoptosis in human gastric epithelial cells. This may result in gastric mucus damage during H. pylori infection.
We further used gene knockout H. pylori strains to investigate H. pylori factors involved in enhanced sensitivity to TRAIL-induced apoptosis in human gastric epithelial cells. Our results showed that the H. pylori virulent factors related genes, cagA、vacA and ureaseB single knockout strains were not able to suppress the H. pylori-induced TRAIL sensitivity in human gastric epithelial cells. We further demonstrated that the H. pylori-induced TRAIL-mediated apoptosis was dependent on direct bacteria contact, indicating that H. pylori adhesion may play an important role in inducing TRAIL sensitivity in human gastric epithelial cells. Since adhesins are essential for adhesion, we further characterize role of genes important in adhesion in inducing TRAIL sensitivity by H. pylori. Our results indicated that H. pylori strains with gene defect in BabA、SabA or HopZ was still intact in induction of TRAIL sensitivity in gastric epithelial cells, indicating that there are other H. pylori factors critical for induction of TRAIL sensitivity in gastric epithelial cells. Further study to explore the possible factors in inducing TRAIL sensitivity is undergoing.
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