Author(s)

Bronislaw L. Slomiany, Amalia Slomiany

Research Center, University of Medicine and Dentistry of New Jersey, Newark, USA.

Disturbances in nitric oxide synthase (NOS) and cyclooxygenase (COX) isozyme systems, manifested by the excessive NO and prostaglandin (PGE₂) generation, are well-recognized features of gastric mucosal inflammatory responses to H. pylori infection. In this study, we report that H. pylori LPS-induced enhancement in gastric mucosal inducible (i) iNOS expression and COX-2 activation was accompanied by the impairment in constitutive (c) cNOS phosphorylation, up-regulation in the inhibitory κB kinase-β (IKKβ) activation and the increase in the transcriptional factor, NF-κB, nuclear translocation. Further, we show that abrogation of cNOS control over NF-κB activation has lead to induction of iNOS expression and COX-2 activation through S-nitrosylation. Moreover, we demonstrate that the modulatory effect of peptide hormone, ghrelin, on the LPS-induced changes was reflected in the increase in Src/Akt-dependent cNOS activation through phosphorylation and the suppression of IKK-β activity through cNOS-mediated IKK-β protein S-nitrosylation. As a result, ghrelin exerted the inhibitory effect on NF-κB nuclear translocation, thus causing the repression of iNOS gene induction and the inhibition in COX-2 activation through iNOS-dependent S-nitrosylation. Our findings point to cNOS activation as a pivotal element in the signaling cascade by which ghrelin exerts modulatory control over proinflammatory events triggered in gastric mucosa by H. pylori infection.

H. pylori; Gastric Mucosa; iNOS Induction; COX-2 Activation; Ghrelin; cNOS Phosphorylation; IKK-β; S-Nitrosylation

Slomiany, B. and Slomiany, A. (2012) Modulation of gastric mucosal inflammatory responses to Helicobacter pylori by ghrelin: Role of cNOS-dependent IKK-β S-nitrosylation in the regulation of COX-2 activation. American Journal of Molecular Biology, 2, 113-123. doi: 10.4236/ajmb.2012.22013.