https://scholars.lib.ntu.edu.tw/handle/123456789/160493
標題: | 胃幽門螺旋桿菌引起TRAIL所誘發之細胞凋亡訊息傳導的調節機轉(2/2) Mechanisms of Helicobacter induced modulation of TRAIL death signal transduction(2/2) |
作者: | 許秉寧 | 關鍵字: | Helicobacter pylori;TRAIL;apoptosis;human gastric epithelial cells;mitochondria | 公開日期: | 2004 | 出版社: | 臺北市:國立臺灣大學醫學院免疫學研究所 | 摘要: | 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. |
URI: | http://ntur.lib.ntu.edu.tw//handle/246246/25364 | 其他識別: | 922320B002160 | Rights: | 國立臺灣大學醫學院免疫學研究所 |
顯示於: | 免疫學研究所 |
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