IL-1-INDUCED NITRIC-OXIDE INHIBITS CHONDROCYTE PROLIFERATION VIA PGE2

IL-1 inhibits chondrocyte proliferation induced by TGF beta or serum, This study analyzed the role of nitric oxide (NO), which is induced at high levels by IL-1 in chondrocytes, NO, when administered through so dium nitroprusside (SNP), inhibited TGF beta or serum-induced chondroc yte proliferation. To determine whether IL-1-induced NO is responsible for growth inhibition by IL-1, chondrocytes were cultured in the pres ence of the nitric oxide synthase inhibitor N-monomethyl-L-arginine (N MA), which dose-dependently reduced the antiproliferative effects of I L-1. Analysis of interactions between PGE2, a known chondrocyte growth inhibitor, and NO showed that PGE2 does not induce NO and is not requ ired for NO induction by IL-1. However, SNP induced high levels of PGE 2, and NMA reduced IL-1-induced PGE2. This raised the possibility that PGE2 is a downstream mediator of the antiproliferative effects of NO, This was confirmed in experiments where the growth inhibitory effects of SNP were reduced by indomethacin, These results suggest that the c hondrocyte growth inhibition by IL-1 in chondrocytes is due to the ind uction of NO, which stimulates the production of PGE2 as a mediator of its antiproliferative effects. (C) 1995 Academic Press, Inc.