15-deoxy-Δ12,14-prostaglandin j2 suppresses rantes expression by inhibiting nadph oxidase activation in helicobacter pylori-infected gastric epithelial cells

Peroxisome proliferators-activated receptor-g (ppar-γ) is a ligand-activated transcription factor. 15 deoxy-12,14 prostaglandin j2 (15d-pgj2) is a potent ppar-γ ligand and acts as an anti-inflammatory agent via ppar-γ-dependent and independent mechanisms. helicobacter pylori (h. pylori) induces gastric inflammation by inducing the activation of oxidant-sensitive transcription factor nf-κb and cytokine expression in gastric epithelial cells. since 15d-pgj2 inhibits nf-κb activation in various cells,it may suppress h. pylori-induced inflammatory signaling and cytokine expression in gastric epithelial cells. the present study aims to determined the effect of 15d-pgj2 on the activation of inflammatory mediators jak/stat (janus kinase/signal transducers and activators of transcription) and induction of cytokine rantes in h. pylori-infected gastric epithelial ags cells. since nadph oxidase is a candidate for the production of reactive oxygen species in h. pylori-infected gastric epithelial cells,we determined the effect of 15d-pgj2 on the activation of nadph oxdase. ags cells were cultured in the presence of h. pylori treated with or without 15d-pgj2. the activations of nadph oxidase and jak1/stat3,the levels of h2o2 and rantes in the medium,and dna binding activity of stat3 were assessed. ajak/stat3 specific inhibitor ag490 and an inhibitor of nadph oxidase diphenyleneiodonium (dpi) were treated to determine the direct involvement of jak/stat and nadph oxidase on the production of h2o2 and rantes in h. pylori-infected cells. h. pylori induced the production of h2o2 and rantes as well as the activations of nadph oxidase and jak1/stat3,which were inhibited by the treatment of 15d-pgj2. dpi suppressed h. pylori-induced alterations similar to 15d-pgj2. however,ag490 had no effect on nadph oxidase activation,but reduced the level of rantes in the medium released from h. pylori-infected cells. conclusion: nadph oxidase activation is an upstream signaling of jak1/stat3 activation and induction of rantes in h. pylori-infected ags cells. 15d-pgj2,inhibits the activations of nadph oxidase and jak1/stat3 and rantes expression,suggesting that 15d-pgj2 may be beneficial for the treatment of h. pylori-induced gastric inflammation.