Helicobacter pylori colonization leads to epithelial cell hyperproliferation within inflamed mucosa, but levels of apoptosis vary, suggesting that imbalances between rates of cell production and loss may contribute to differences in gastric cancer risk among infected populations. Peroxisome proliferator-activated receptor γ (PPARγ) regulates inflammatory and growth responses of intestinal epithelial cells. We determined whether activation of PPARγ modified H. pylori-induced apoptosis in gastric epithelial cells. PPARγ was expressed and functionally active in gastric epithelial cell lines sensitive to H. pylori-induced apoptosis. PPARγ ligands 15d-PGJ2 and BRL-49653 significantly attenuated H. pylori-induced apoptosis, effects that could be reversed by co-treatment with a specific PPARγ antagonist. Cyclopentanone prostaglandins that do not bind and activate PPARγ had no effects on H. pylori-induced apoptosis. The ability of H. pylori to activate nuclear factor (NF)-γB and increase levels of the NF-γB target IL-8 was blocked by co-treatment with PPARγ agonists, and direct inhibition of NF-γB also abolished H. pylori-stimulated apoptosis. These results suggest that activation of the PPARγ pathway attenuates the ability of H. pylori to induce NF-γB-mediated apoptosis in gastric epithelial cells. Because PPARγ regulates a multitude of host responses, activation of this receptor may contribute to varying levels of cellular turnover as well as the diverse pathologic outcomes associated with chronic H. pylori colonization.
|Original language||English (US)|
|Number of pages||8|
|Journal||Journal of Biological Chemistry|
|State||Published - Aug 17 2001|
ASJC Scopus subject areas
- Molecular Biology
- Cell Biology