Cyclooxygenase-2 S-nitrosylation in salivary gland acinar cell inflammatory responses to <i>Porphyromonas gingivalis</i>: modulatory effect of ghrelin — Oak Academic Publishing
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Cyclooxygenase-2 S-nitrosylation in salivary gland acinar cell inflammatory responses to <i>Porphyromonas gingivalis</i>: modulatory effect of ghrelin
Disturbances in nitric oxide synthase (NOS) system and the excessive prostaglandin (PGE<sub>2</sub>) generation are well-recognized features of oral mucosal inflammatory responses to periodontopathic bacterium, <i>P. gingivalis</i>. Employing rat sublingual gland acinar cells, we show that <i>P. gingivalis</i> LPS-induced up-regulation in PGE<sub>2</sub> 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 PGE<sub>2</sub> 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 <i>P. gingivalis</i>-induced up-regulation in iNOS leads to COX-2 S-nitrosylation and up-regulation in PGE<sub>2</sub> 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.
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