Involvement of p38 MAPK-dependent activator protein (AP-1) activation in modulation of gastric mucosal inflammatory responses to Helicobacter pylori by ghrelin

B. L. Slomiany, A. Slomiany

Research output: Contribution to journalArticlepeer-review

30 Scopus citations

Abstract

A peptide hormone, ghrelin, plays an important role in modulation of gastric mucosal inflammatory responses to Helicobacter pylori infection by controlling the cross-talk between nitric oxide synthase (NOS) and cyclooxygenase (COX) enzyme systems. In this study, we report that H. pylori LPS-elicited induction in gastric mucosal COX-2 and inducible (i) iNOS protein expression, and the impairment in constitutive (c) cNOS phosphorylation, was associated with mitogen-activated protein kinase, c-Jun N-terminal kinase (JNK), extracellular signalregulated kinase and p38 activation, and occurred with the involvement of transcription factors, CCATT/enhancerbinding protein (C/EBP) d, cAMP response element-binding protein, activator protein-1 (AP-1), and NF-jB. The modulatory effect of ghrelin on the LPS-induced changes was manifested in the inhibition of nuclear translocation of p65 NF-jB and C/EBPd, and suppression in AP-1 activation, and the inhibition in phosphorylation of JNK and p38, as well as their respective downstream targets, c-Jun and ATF-2. However, only the inhibition of p38-mediated ATF-2 phosphorylation was reflected in the reduced expression of COX-2 protein. Further, the effect of ghrelin of the LPS-induced changes was reflected in the increase in Src/Akt-dependent cNOS activation through phosphorylation and the inhibition of cNOS-mediated IKK-b S-nitrosylation. Our findings indicate ghrelin counters the proinflammatory consequences of H. pylori by interfering with the p38/ATF-2-induced AP-1 activation in association with concurrent up-regulation in Src/Akt-dependent cNOS phosphorylation.

Original languageEnglish (US)
Pages (from-to)67-78
Number of pages12
JournalInflammopharmacology
Volume21
Issue number1
DOIs
StatePublished - Feb 2013

All Science Journal Classification (ASJC) codes

  • Immunology
  • Pharmacology
  • Pharmacology (medical)

Keywords

  • AP-1
  • COX
  • Gastric mucosa
  • Ghrelin
  • H. pylori
  • NF-jB
  • NOS
  • P38 kinase
  • S-nitrosylation

Fingerprint

Dive into the research topics of 'Involvement of p38 MAPK-dependent activator protein (AP-1) activation in modulation of gastric mucosal inflammatory responses to Helicobacter pylori by ghrelin'. Together they form a unique fingerprint.

Cite this