NITRIC-OXIDE AND PROTEOGLYCAN BIOSYNTHESIS BY HUMAN ARTICULAR CHONDROCYTES IN ALGINATE CULTURE

Interleukin-1 alpha, and beta induced the production of large amounts of nitric oxide by normal, human articular chondrocytes in alginate culture; at the same time the biosynthesis of proteoglycan was strongly suppressed. In a dose-dependent manner, N-G-monomethyl-L-arginine both inhibited nitric oxide formation and relieved the suppression of proteoglycan synthesis. However concentrations of N-G-monomethyl-L-arginine which completely prevented nitric oxide production only partially restored proteoglycan biosynthesis, even at low doses of interleukin-1 where suppression of proteoglycan synthesis was modest. The organic donor of nitric oxide, S-nitrosyl-acetyl-D,L-penicillamine also inhibited proteoglycan biosynthesis, but not as extensively as interleukin-1. These data suggest that interleukin-1 suppresses synthesis of the cartilaginous matrix through more than one mechanism, at least one of which is dependent upon the production of nitric oxide.