Helicobacter pylori Induction in Gastric Mucosal Prostaglandin and Nitric Oxide Generation Is Dependent on MAPK/ERK-Mediated Activation of IKK-β and cPLA2: Modulatory Effect of Ghrelin

摘要: Among the key factors defining extent of gastric mucosal inflammatory involvement in response to H. pylori is excessive generation prostaglandin (PGE2) and nitric oxide (NO), caused by overexpression cyclooxygenase-2 (COX-2) inducible synthase (iNOS), triggered activation MAPK/JNK, p38 ERK, nuclear translocation cognate transcription factors. In this study, we report on role MAPK/ERK regulation LPS-induced expression COX-2 iNOS. We show that ERK LPS leads phosphorylation inhibitory κB kinase-β (IKK-β) cytosolic phospholipase A2 (cPLA2), reflected upsurge NF-κB translocation, induction iNOS expression, up-regulation cPLA2 activity. The modulatory effect peptide hormone, ghrelin, changes, although associated with further enhancement IKK-β phosphorylation, was suppression activity through S-nitrosylation. While ghrelin S-nitrosylation susceptible inhibitors Src/Akt pathway, inhibition blockage as well Taken together, our data pylori-induced plays a critical PGE2 NO at level activation, counters these proinflammatory consequences Src/Akt-dependent