INTERFERON-GAMMA DIFFERENTIALLY AFFECTS THE SYNTHESIS OF CHONDROITIN DERMATAN SULFATE AND HEPARAN-SULFATE BY HUMAN SKIN FIBROBLASTS/

Interferon gamma (IFN gamma) is often considered to be an antifibrotic cytokine because it inhibits collagen synthesis in fibroblasts. Here we report the effects of recombinant human IFN gamma on sulphated glyc osaminoglycan chains produced by normal skin fibroblasts from adult do nors. IFN gamma (250 i.u./ml) induced an increase in incorporation of D-[1-H-3]glucosamine into glycosaminoglycans, either secreted into the culture medium or associated with the cell layer. The structures of t hese molecules were analysed by using various cleavage agents (heparin ases I and II, heparitinase/chondroitinases ABC and AC/periodate oxida tion) followed by size-exclusion and anion-exchange HPLC. No modificat ion was detected in the structure of the heparan sulphate chains. In c ontrast, the cytokine induced changes in the microcomposition of chond roitin/dermatan sulphate chains. More precisely, we found a decrease i n the iduronic acid content, associated with down-regulation of the 4- O-sulphation on the GalNAc residues. In contrast, the 6-O-sulphation o n these GalNAc residues was potentiated by the cytokine. These results indicate that IFN gamma is able to modulate not only collagen but als o the structure of galactosaminoglycans synthesized by human skin fibr oblasts.