Toxicity of Helicobacter pylori VacA and its mutual effect with CagA

点击翻译按钮获取中文摘要

1) VacA may induce apoptosis by downregulation of anti-apoptotic Bcl-2 subfamily proteins via STAT3 inhibition. 2) VacA enhances PGE2 production by AZ-521 cells through induction of COX-2 expression via the p38 MAPK/ATF-2 cascade, leading to activation of the CRE site in the COX-2 promoter. 3) In promonocytic U937 cells, VacA directly increases IL-8 production by activation of the p38 MAPK via intracellular Ca^<2+> release, leading to activation of the transcription factors, ATF-2, CREB, and NF-kB. 4) VacA stimulated protein kinase B (Akt) activity via activation of PI3K, resulting in increased phosphorylation of its substrate, GSK3, with subsequent release of ■-catenin from a GSK3/■-catenin complex and its translocation to the nucleus, leading to activation of the cyclin D1 promoter. 5) Translocated CagA from H. pylori into gastric epithelial cells inhibit uptake and cytotoxicity of VacA via endocytosis inhibition in the cells. However, transfection of cagA gene did not affect the activation of p38 MAPK caused by VacA.