|Budget Amount *help
¥4,200,000 (Direct Cost: ¥4,200,000)
Fiscal Year 2002: ¥1,600,000 (Direct Cost: ¥1,600,000)
Fiscal Year 2001: ¥2,600,000 (Direct Cost: ¥2,600,000)
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 cytokines
On 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.