title: Suppression of gastric mucosal inflammatory responses to Helicobacter pylori lipopolysaccharide by peroxisome proliferator-activated receptor gamma activation.
abstract: Peroxisome proliferator-activated receptor-gamma (PPAR-gamma) 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 PPAR-gamma 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 PPAR-gamma activation suppresses gastric mucosal inflammatory responses to H. pylori LPS, and suggest that pharmacological manipulation of PPAR-gamma activation may provide therapeutic benefits in the resolution of inflammation associated with H. pylori infection.
authors.affiliation: Research Center, University of Medicine and Dentistry of New Jersey, Newark, New Jersey 07103-2400, USA. slomiabr@umdnj.edu
authors.forename: Bronislaw L
authors.initials: BL
authors.lastname: Slomiany
authors.forename: Amalia
authors.initials: A
authors.lastname: Slomiany
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D051546:Cyclooxygenase 2; D005753:Gastric Mucosa / Q000187:drug effects* / Q000378:metabolism* / Q000473:pathology; D005756:Gastritis / Q000209:etiology* / Q000378:metabolism / Q000517:prevention & control*; D016480:Helicobacter pylori / Q000472:pathogenicity*; D007249:Inflammation / Q000209:etiology / Q000378:metabolism / Q000517:prevention & control; D007527:Isoenzymes / Q000378:metabolism; D008024:Ligands; D008070:Lipopolysaccharides / Q000633:toxicity*; D019001:Nitric Oxide Synthase / Q000378:metabolism; D052247:Nitric Oxide Synthase Type II; D011451:Prostaglandin-Endoperoxide Synthases / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D018160:Receptors, Cytoplasmic and Nuclear / Q000378:metabolism*; D013844:Thiazoles / Q000378:metabolism / Q000494:pharmacology; D045162:Thiazolidinediones; D014157:Transcription Factors / Q000378:metabolism*
chemical_list: D007527:Isoenzymes; D008024:Ligands; D008070:Lipopolysaccharides; D018160:Receptors, Cytoplasmic and Nuclear; D013844:Thiazoles; D045162:Thiazolidinediones; D014157:Transcription Factors; D019001:Nitric Oxide Synthase; D052247:Nitric Oxide Synthase Type II; C496318:Nos2 protein, rat; D051546:Cyclooxygenase 2; D011451:Prostaglandin-Endoperoxide Synthases; C039671:ciglitazone