Interleukin-4 and interferon-gamma inhibit prostaglandin production by interleukin-1 beta-stimulated human periodontal ligament fibroblasts

The purpose of the present study was to investigate the involvement of cycl ooxygease-1 (COX-1) and cyclooxygenase-2 (COX-2) in prostaglandin (PG) prod uction by human periodontal ligament (PDL) fibroblasts stimulated with a pr oinflammatory cytokine, ineterleukin-1 beta (IL-1 beta), and to examine the effect of interleukin-4 (IL-4), a Th2 cytokine, and interferon-gamma (IFN- gamma), a Th1 cytokine, on PG production by the cells. IL-1 beta-stimulated PDL fibroblasts produced prostaglandin E-2 (PGE(2)) in a time-dependent ma nner. Indomethacin, a non-selective COX-1/COX-2 inhibitor, and NS-398, a se lective COX-2 inhibitor, completely inhibited PGE(2) production by IL-1 bet a-stimulated cells. Northern blot analysis showed that COX-2 mRNA was detec ted in IL-1 beta-stimulated PDL cells, although not detected in unstimulate d cells, while expression of COX-1 mRNA was in the same extent in both the cells. Dexamethasone inhibited COX-2 mRNA expression, COX activity and PGE( 2) production in IL-1 beta-stimulated cells. IL-4 and IFN-gamma suppressed PGE(2) production by IL-1 beta-stimulated PDL fibroblasts, but COX activity enhanced by IL-1 beta treatment was significantly inhibited by IL-4, not b y IFN-gamma. Northern blot analysis showed that IL-4 depressed COX-2 mRNA e xpression with no effect on COX-1 mRNA expression. On the other hand, IFN-g amma had no effect on expression of COX-1 and -2 mRNA. These data suggest t hat COX-2 is primarily responsible for PGE(2) production by IL-l beta-stimu lated human PDL fibroblasts and that IL-4 inhibited PGE? production by IL-1 beta-stimulated PDL fibroblasts through down-regulation of COX-2 expressio n, while IFN-gamma suppressed the PGE(2) production with no effect on COX-2 expression.