Helicobacter pylori-induced prostaglandin E2 synthesis involves activation of cytosolic phospholipase A2 in epithelial cells

Abstract

Helicobacter pylori initiates an inflammatory response and gastric diseases, which are more common in patients infected with H. pylori strains carrying the pathogenicity island, by colonizing the gastric epithelium. In the present study we investigated the mechanism of prostaglandin E2 (PGE2) synthesis in response to H. pylori infection. We demonstrate that H. pylori induces the synthesis of PGE2 via release of arachidonic acid predominately from phosphatidylinositol. In contrast to H. pylori wild type, an isogenic H. pylori strain with a mutation in the pathogenicity island exerts only weak arachidonic acid and PGE2 synthesis. The H. pylori-induced arachidonic acid release was abolished by phospholipase A2 (PLA2) inhibitors and by pertussis toxin (affects the activity of Gαi/Gαo). The role of phospholipase C, diacylglycerol lipase, or phospholipase D was excluded by using specific inhibitors. An inhibitor of the stress-activated p38 kinase (SB202190), but neither inhibitors of protein kinase C nor an inhibitor of the extracellular-regulated kinase pathway (PD98059), decreased the H. pylori-induced arachidonic acid release. H. pylori-induced phosphorylation of p38 kinase and cytosolic PLA2 was blocked by SB202190. These results indicate that H. pylori induces the release of PGE2 from epithelial cells by cytosolic PLA2 activation via Gαi/Gαo proteins and the p38 kinase pathway.