INTERLEUKIN-1 INDUCED NITRIC-OXIDE INHIBITS SULFATION OF GLYCOSAMINOGLYCAN CHAINS IN HUMAN ARTICULAR CHONDROCYTES

Incubation of human articular cartilage explants with interleukin-1 al pha (IL-1 alpha) inhibited the rate of [S-35]sulphate incorporation in to glycosaminoglycan (GAG) chains concomitant with an increase in nitr ic oxide (NO) production. Measurement of the [S-35]sulphate showed tha t IL-1 alpha inhibited the synthesis of both keratan sulphate and chon droitin sulphate (CS) chains to a similar extent. This effect was reve rsed by the NO synthase inhibitor N-omega-iminoethyl-L-ornithine (L-NI O). Analysis of alkali borohydride cleaved GAG chains showed that IL-1 alpha had no effect on their size. Similarly when GAG chains were cou pled to xyloside the size of the GAG chains attached to the exogenous acceptor decreased but IL-1 alpha had no further effect on hydrodynami c size. IL-1 alpha did, however, inhibit [S-35]sulphate incorporation into xyloside-linked CS chains. In both experiments L-NIO reversed the inhibitory effect on sulphation. Disaccharide analysis of the [S-35]G AG chains showed that IL-1 alpha preferentially inhibited sulphation o f the 6-sulphated isomer and that L-NIO reversed this effect. Thus, IL -1 alpha-induced NO mediates the inhibition of sulphate incorporation and alters the sulphation pattern of newly synthesised GAG chains. (C) 1998 Elsevier Science B.V. All rights reserved.