Regulation of prostaglandin E_2 synthesis by sphingolipids in human gingival fibroblasts

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Ceramide is an integral component of sphingolipids signaling pathway, which acts as second messenger in cellular process such as inflammation, cell proliferation, and apoptosis in number of cell types. In this study, we investigated the effects of the cell permeable ceramide (a series of ceramide analog with acyl chain length of 2, 6, 8 and 16 on the) on prostaglandin E_2 synthesis and cyclooxgenas&2mRNA expression, a rate-limiting enzyme for the conversion of arachidonic acid to prostanoids in human gingival fibroblasts.Methods : Human gingival fibroblasts was obtained from explants of human gingival tissue. Prostaglan-dinE_2 release was determined by an enzyme-immunoassay. Cyclooxgenase-2mRNA levels was detected by RT-PCR.Results : Cell permeable ceramide by itself did not induced prostaglandinE_2 synthesis. The only treated with C_2-ceramide, IL-1β-induced prostaglandinE_2 release was inhibited in a dose-and time-dependent manner, whereas C_2-ceramide enhanced IL-1β-stimulated cyclooxgenase-2mRNA expression. C_2-dehydroceramide, a biologically inactive C2-ceramide analog, did not affect both IL-1β-induced prostaglandinE_2 release and cyclooxgenase-2mRNA expression. In contrast, the other long chain ceramide potentiated IL-1β-stimulated prostaglandinE_2 production. The most effective C_<16>-ceramide enhanced prostaglandinE_2 production by 60%. of control. These results indicate that effect of cell permeable ceramide analog on prostaglandinE_2 production depends on N-acyl chain length. C_2-ceramide inhibits the IL-1β-induced prostaglandinE_2 synthesis, but which appears not to be due to the decrease of Cyclooxgenase-2mRNA expression. These results suggest that the modulation on the C_2-ceramide signaling pathway may offer a therapeutic approach for inhibiting cyclooxgenase-2 activity, such as periodontal diseases.