Effect of prostaglandin E_2 on matrix metalloproteinase-3 production in human periodontal ligament cells stimulated with interleukin-1α

Objective To investigate whether COX-2-derived PGE2 regulates matrix metalloproteinase(MMP)-3 production in human periodontal ligament(PDL) cells stimulated with interleukin(IL)-1α.Methods Human PDL cells obtained from periodontally healthy subjects were stimulated with vehicle or IL-1α in the presence or absence of indomethacin(a COX-1/COX-2 inhibitor),NS-398(a specific COX-2 inhibitor),and PGE2.PGE2 levels were assayed by enzyme-linked immunosorbent assay(ELISA).MMP-3 levels and caseinolytic activities were evaluated by ELISA and casein zymography,respectively.Results IL-1α enhanced both MMP-3 and PGE2 production.Indomethacin and NS-398 enhanced IL-1α-induced MMP-3 production in PDL cells,to the same extent,although both the agents completely inhibited IL-1α-induced PGE2 production.Exogenous PGE2 reduced IL-1α-induced MMP-3 production in a dose-dependent manner.Conclusion COX-2-dependent PGE2 downregulates IL-1α-elicited MMP-3 production.