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TOXICITY OF HELICOBACTER PYLORI VACA TOXIN THROUGH ITS CELLULAR RECEPTOR

幽门螺杆菌毒素通过其细胞受体的毒性

基本信息

批准号：
13670276
负责人：
HIRAYAMA Toshiya
金额：
$ 2.69万
依托单位：
NAGASAKI UNIVERSITY
依托单位国家：
日本
项目类别：
Grant-in-Aid for Scientific Research (C)
财政年份：
2001
资助国家：
日本
起止时间：
2001 至 2002
项目状态：
已结题

来源：
https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-13670276/
关键词：
Helicobacter Vacuolating cytotoxin VacA Toxicity Bacterial toxin toxin receptor RPTP β

项目摘要

H. pylori VacA might be at least one factor causing the cell death by apoptosis, that is observed in H. Pylori infection. To elucidate the function of p38 in the damage of VacA-treated cells, we examined the effect of VacA on phosphorylation of p38 MAP kinase. VacA stimulated p38 phosphorylation in a concentration-dependent manner. The p38 inhibitor, SB203580, at concentration of 10μM did not inhibit VacA-induced cellular vacuolation, decrease in mitochondrial Membrane potential, or cytochrome C release from mitochondria. These results are consistent with the notion that p38 signaling pathway might not contribute to cell death.Also, to examine the mechanisms of inflammation in H. pylori-induced gastritis, we administered VacA to the mice. Inoculation of VacA resulted in epithelium vacuolization and marked infiltrations of mast cells and mononuclear cells into the mucosal epithelium. In addition, VacA induced bone marrow-derived mast cells to produce proinflammatory cytokinesOn the other hand, VacA binds to its cell surface receptor, receptor tyrosine phosphatase (RPTP) β, leading to cytoplasmic vacuolization of gastric epithelial AZ-521 cells. VacA binding to the cell surface and VacA-dependent vacuolization were inhibited by cell culture media containing fetal calf serum (PCS). These data show that the high molecular weight fraction of FCS inhibits VacA action though its ability to block toxin binding to its receptor, RPTPβ, on AZ-521 cells.

H. pylori VacA可能是导致细胞凋亡的至少一个因素，在H.幽门感染。为了阐明p38在VacA处理的细胞损伤中的作用，我们检测了VacA对p38 MAP激酶磷酸化的影响。VacA以浓度依赖性方式刺激p38磷酸化。浓度为10μM的p38抑制剂SB 203580未抑制VacA诱导的细胞空泡化、线粒体膜电位降低或线粒体释放细胞色素C。这些结果与p38信号通路可能不参与细胞死亡的观点一致。pylori诱导的胃炎，我们给小鼠施用VacA。接种VacA导致上皮空泡化，肥大细胞和单核细胞明显浸润到粘膜上皮中。另外，VacA还可诱导骨髓来源的肥大细胞产生促炎细胞因子，另一方面，VacA与其细胞表面受体酪氨酸磷酸酶（RPTP）β结合，导致胃上皮AZ-521细胞胞浆空泡化。含有胎牛血清（PCS）的细胞培养基可抑制VacA与细胞表面的结合和VacA依赖的空泡化。这些数据表明，FCS的高分子量部分通过其阻断毒素与AZ-521细胞上的受体RPTPβ结合的能力抑制VacA作用。