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  • Title: Protein kinase Cdelta-mediated CREB activation regulates ghrelin-induced cyclooxygenase-2 expression and prostaglandin E2 production in human colonic epithelial cells.
    Author: Zhao D.
    Journal: J Cell Biochem; 2007 Dec 01; 102(5):1245-55. PubMed ID: 17455223.
    Abstract:
    Ghrelin, a newly identified gastric peptide, is known for its potent activity in growth hormone release and appetite. Our recent study showed that ghrelin could stimulate protein kinase C-mediated activation of nuclear factor-kappaB (NF-kappaB) and interleukin-8 secretion in human colonic epithelial cells transfected with a functional ghrelin receptor. In the present study, the effect of ghrelin stimulation on cyclooxygenese-2 expression and prostaglandin E2 production was examined. The data indicate that ghrelin significantly increased the levels of cyclooxygenase-2 (COX-2) protein as well as its promoter activity, which leaded to profound increase in prostaglandin E2 secretion. In order to examine the involvement of NF-kappaB and cAMP responsive element-binding protein (CREB) in this response, the NF-kappaB inhibitory protein IkappaBalpha or a dominant negative mutant of CREB was co-transfected into cells and the data show that transfection of either IkappaBalpha or DN-CREB significantly attenuated ghrelin-induced COX-2 expression. Moreover ghrelin stimulated phosphorylation of CREB, which was mediated primarily via protein kinase Cdelta activation. Furthermore, inhibition of PKCdelta function significantly attenuated ghrelin-induced COX-2 expression. In addition, ghrelin stimulates phosphorylation of PKCdelta. Together, these results indicate that in addition to NF-kappaB, protein kinase Cdelta-mediated CREB activation plays an important role in the cellular responses of ghrelin.
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