Open AccessTumor Necrosis Factor Alpha and Interleukin 1β Up-Regulate Gastric Mucosal Fas Antigen Expression inHelicobacter pyloriInfection
Author(s) -
JeanMarie Houghton,
Lisa S. Macera-Bloch,
Lawrence E. Harrison,
Kyung H. Kim,
Reju Korah
Publication year - 2000
Publication title -
infection and immunity
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.508
H-Index - 220
eISSN - 1070-6313
pISSN - 0019-9567
DOI - 10.1128/iai.68.3.1189-1195.2000
Subject(s) - fas ligand , biology , apoptosis , helicobacter pylori , tumor necrosis factor alpha , immune system , peripheral blood mononuclear cell , immunology , antigen , fas receptor , interleukin , cytokine , programmed cell death , in vitro , biochemistry , genetics
Fas-mediated gastric mucosal apoptosis is gaining attention as a cause of tissue damage due toHelicobacter pylori infection. We explored the effects ofH. pylori directly, and the effects of the inflammatory environment established subsequent toH. pylori infection, on Fas-mediated apoptosis in a nontransformed gastric mucosal cell line (RGM-1). Exposure toH. pylori -activated peripheral blood mononuclear cells (PBMCs), but notH. pylori itself, induced Fas antigen (Fas Ag) expression, indicating a Fas-regulatory role for inflammatory cytokines in this system. Of various inflammatory cytokines tested, only interleukin 1β and tumor necrosis factor alpha induced Fas Ag expression, and removal of either of these from the conditioned medium abrogated the response. When exposed to Fas ligand, RGM-1 cells treated with PBMC-conditioned medium underwent massive and rapid cell death, interestingly, with a minimal effect on total cell numbers early on. Cell cycle analysis revealed a substantial increase in S phase cells among cells exposed to Fas ligand, suggesting an increase in their proliferative response. Taken together, these data indicate that the immune environment secondary toH. pylori infection plays a critical role in priming gastric mucosal cells to undergo apoptosis or to proliferate based upon their Fas Ag status.