Suppression of gastric mucosal inflammatory responses to Helicobacter pylori lipopolysaccharide by peroxisome proliferator-activated receptor γ activation

Abstract

Peroxisome proliferator-activated receptor-γ (PPARγ) is a nuclear transcription factor that regulates the expression of genes associated with inflammation. We applied the animal model of H. pylori lipopolysaccharide(LPS)-induced gastritis to assess the effect of a specific PPARγ ligand, ciglitazone, on the apoptotic processes and the mucosal activity of inducible nitric oxide synthase (NOS-2), and the expression of COX-1 and -2 cyclooxygenases. In the absence of ciglitazone, the LPS-elicited mucosal inflammatory responses were accompanied by a massive epithelial cell apoptosis, upregulation of NOS-2 and COX-2 protein expression, and a marked increase in the mucosal PGE2 generation and NOS-2 activity. The expression of COX-1 protein, however, remained unchanged. Administration of ciglitazone led to dose-dependent reduction (up to 48%) in the severity of mucosal inflammatory involvement elicited by the LPS and this effect of the agent was reflected in a 72.5% reduction in apoptosis, a 58.7% decline in the mucosal PGE2 generation and a 75.6% drop in NOS-2 activity, and produced a marked decrease inCOX-2 and NOS-2 protein expression. Our findings demonstrate that PPARγ activation suppresses gastric mucosal inflammatory responses to H. pylori LPS, and suggest that pharmacological manipulation of PPARγ activation may provide therapeutic benefits in the resolution of inflammation associated with H. pylori infection.