Activation of Peroxisome Proliferator-activated Receptor γ Suppresses Nuclear Factor κB-mediated Apoptosis Induced by Helicobacter pylori in Gastric Epithelial Cells

Rajnish A. Gupta, D. Brent Polk, Uma Krishna, Dawn A. Israel, Fang Yan, Raymond N. DuBois, Richard M. Peek

Research output: Contribution to journalArticlepeer-review

101 Scopus citations

Abstract

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 languageEnglish (US)
Pages (from-to)31059-31066
Number of pages8
JournalJournal of Biological Chemistry
Volume276
Issue number33
DOIs
StatePublished - Aug 17 2001
Externally publishedYes

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology
  • Cell Biology

Fingerprint

Dive into the research topics of 'Activation of Peroxisome Proliferator-activated Receptor γ Suppresses Nuclear Factor κB-mediated Apoptosis Induced by Helicobacter pylori in Gastric Epithelial Cells'. Together they form a unique fingerprint.

Cite this