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

Abstract

The purpose of the present study was to investigate the involvement of cyclooxygease-1 (COX-1) and cyclooxygenase-2 (COX-2) in prostaglandin (PG) production by human periodontal ligament (PDL) fibroblasts stimulated with a proinflammatory cytokine, inerleukin-1beta (IL-1beta), 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-1beta-stimulated PDL fibroblasts produced prostaglandin E2 (PGE2) in a time-dependent manner. Indomethacin, a non-selective COX-1/COX-2 inhibitor, and NS-398, a selective COX-2 inhibitor, completely inhibited PGE2 production by IL-1beta-stimulated cells. Northern blot analysis showed that COX-2 mRNA was detected in IL-1beta-stimulated PDL cells, although not detected in unstimulated 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 PGE2 production in IL-1beta-stimulated cells. IL-4 and IFN-gamma suppressed PGE2 production by IL-1beta-stimulated PDL fibroblasts, but COX activity enhanced by IL-1beta treatment was significantly inhibited by IL-4, not by IFN-gamma. Northern blot analysis showed that IL-4 depressed COX-2 mRNA expression with no effect on COX-1 mRNA expression. On the other hand, IFN-gamma had no effect on expression of COX-1 and -2 mRNA. These data suggest that COX-2 is primarily responsible for PGE2 production by IL-1beta-stimulated human PDL fibroblasts and that IL-4 inhibited PGE2 production by IL-1beta-stimulated PDL fibroblasts through down-regulation of COX-2 expression, while IFN-gamma suppressed the PGE2 production with no effect on COX-2 expression.