TITLE:
Cyclooxygenase-2 S-nitrosylation in salivary gland acinar cell inflammatory responses to Porphyromonas gingivalis: modulatory effect of ghrelin
AUTHORS:
Bronislaw L. Slomiany, Amalia Slomiany
KEYWORDS:
Salivary Gland; P. gingivalis; iNOS Induction; COX-2 Activation; S-nitrosylation; Ghrelin; cNOS Phosphorylation
JOURNAL NAME:
Advances in Bioscience and Biotechnology,
Vol.2 No.6,
December
5,
2011
ABSTRACT: Disturbances in nitric oxide synthase (NOS) system and the excessive prostaglandin (PGE2) generation are well-recognized features of oral mucosal inflammatory responses to periodontopathic bacterium, P. gingivalis. Employing rat sublingual gland acinar cells, we show that P. gingivalis LPS-induced up-regulation in PGE2 generation and the enhancement in inducible (i) iNOS activity was associated with COX-2 activation through S-nitrosylation, and accompanied by the suppression in cSrc activity and the impairment in constitutive (c) cNOS phosphorylation. Further, we demonstrate that the countering effect of peptide hormone, ghrelin, on the LPS-induced changes was reflected in the increased cNOS activation through phosphorylation, repression in iNOS induction, and the reduction in PGE2 generation associated with the loss of COX-2 protein S-nitrosylation. Moreover, the effect of ghrelin on cNOS phosphorylation and the LPS-induced COX-2 S-nitrosylation was susceptible to the blockage by cSrc inhibition. Our findings suggest that P. gingivalis-induced up-regulation in iNOS leads to COX-2 S-nitrosylation and up-regulation in PGE2 generation, and that the countering effect of ghrelin is mediated through Src-dependent cNOS activation that is obligatory for the maintenance of iNOS gene suppression.