Abstract
Ghrelin, a peptide hormone, newly identified in oral mucosal tissue, has emerged re-cently as a principal modulator of the in-flammatory responses to bacterial infection through the regulation of nitric oxide syn-thase system. In this study, using rat sub-lingual salivary gland acinar cells, we report that lipopolysaccharide (LPS) of periodon-topathic bacterium, P. gingivalis- induced enhancement in the activity of inducible ni-tric oxide synthase (iNOS) was associated with the suppression in Akt kinase activity and the impairment in constitutive (c) cNOS phosphorylation. Further, we show that the detrimental effect of the LPS on Akt activa-tion, manifested in the kinase protein S-nitrosylation and a decrease in its phos-phorylation at Ser473, was susceptible to suppression by iNOS inhibitor, 1400W. Moreover, we demonstrate that a peptide hormone, ghrelin, countered the LPS- induced changes in Akt activity and NOS system. This effect of ghrelin was reflected in the decreased in Akt S-nitrosylation and the increase in its phosphorylation at Ser473, as well as cNOS activation through phos-phorylation. Our findings suggest that P. gingivalis-induced up-regulation in iNOS leads to Akt kinase inactivation through S-nitrosylation that impacts cNOS activation through phosphorylation. We also show that the countering effect of ghrelin on P. gingivalis-induced disturbances in Akt ac-tivation are manifested in a decrease in the kinase S-nitrosylation and the increase in its phosphorylation.
Highlights
Recent advances in understanding the nature of factors that influence the extent of mucosal inflammatory responses along the alimentary tract, including that of oral cavity, have brought to focus the importance of a peptide hormone, ghrelin [1,2,3,4]
As the oral mucosal inflammatory responses to periodontopathic bacterium, P. gingivalis, are characterized by the disturbances in nitric oxide (NO) production, and since Akt kinase plays a major role in the regulation of nitric oxide synthase (NOS) isozyme system [8,15,22,23], in this study we investigated the effect of P. gingivalis, key virulence factor, LPS, on the processes associated with the activation of kinase Akt in sublingual salivary gland acinar cells
To investigate the role of Akt activation in the disturbances in NO production associated with oral mucosal inflammatory responses to periodontopathic bacterium, P. gingivalis, we used rat sublingual gland acinar cells exposed to the bacterium key virulence factor, LPS
Summary
Recent advances in understanding the nature of factors that influence the extent of mucosal inflammatory responses along the alimentary tract, including that of oral cavity, have brought to focus the importance of a peptide hormone, ghrelin [1,2,3,4] This 28-amino acid peptide, initially isolated from the stomach [1,2], and more recently identified in oral mucosa, saliva and the acinar cells of salivary glands [3], has emerged as a principal modulator of the local inflammatory responses to bacterial infection through the regulation of nitric oxide synthase (NOS) system responsible for nitric oxide (NO) production [5,6,7,8]. Sustained iNOS activation associated with persistence of inflammatory stimulus, is known to have cytotoxic consequences reflected in transcriptional disturbances and the induction of apoptosis [9,11,12,14]
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