Tumor necrosis factor alpha and interleukin 1 beta up-regulate gastric mucosal Fas antigen expression in Helicobacter pylori infection

Fas-mediated gastric mucosal apoptosis is gaining attention as a cause of t issue damage due to Helicobacter pylori infection. We explored the effects of H. pylori directly, and the effects of the inflammatory environment esta blished subsequent to H. pylori infection, on Fas-mediated apoptosis in a n ontransformed gastric mucosal cell line (RGM-1). Exposure to H. pylori-acti vated peripheral blood mononuclear cells (PBMCs), but not H. pylori itself, induced Fas antigen (Fas Ag) expression, indicating a Fas-regulatory role for inflammatory cytokines in this system. Of various inflammatory cytokine s tested, only interleukin 1 beta and tumor necrosis factor alpha induced F as Ag expression, and removal of either of these from the conditioned mediu m abrogated the response. When exposed to Fas ligand, RGM-1 cells treated w ith PBMC-conditioned medium underwent massive and rapid cell death, interes tingly, with a minimal effect on total cell numbers early on. Cell cycle an alysis revealed a substantial increase in S phase cells among cells exposed to Fas ligand, suggesting an increase in their proliferative response. Tak en together, these data indicate that the immune environment secondary to H . pylori infection plays a critical role in priming gastric mucosal cells t o undergo apoptosis or to proliferate based upon their Fas Ag status.