Helicobacter pylori-induced prostaglandin E(2) synthesis involves activation of cytosolic phospholipase A(2) in epithelial cells

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 E(2) (PGE(2)) synthesis in response to H. pylori infection. We demonstrate that H. pylori induces the synthesis of PGE(2) 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 PGE(2) synthesis. The H. pylori-induced arachidonic acid release was abolished by phospholipase A(2) (PLA(2)) inhibitors and by pertussis toxin (affects the activity of G alpha(i)/G alpha(o)). 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 PLA(2) was blocked by SB202190. These results indicate that H. pylori induces the release of PGE(2) from epithelial cells by cytosolic PLA(2) activation via G alpha(i)/G alpha(o) proteins and the p38 kinase pathway.