Interferon γ differentially affects the synthesis of chondroitin/dermatan sulphate and heparan sulphate by human skin fibroblasts

Abstract

Interferon γ (IFNγ) is often considered to be an antifibrotic cytokine because it inhibits collagen synthesis in fibroblasts. Here we report the effects of recombinant human IFNγ on sulphated glycosaminoglycan chains produced by normal skin fibroblasts from adult donors. IFNγ (250 i.u./ml) induced an increase in incorporation of D-[1-3H]glucosamine into glycosaminoglycans, either secreted into the culture medium or associated with the cell layer. The structures of these molecules were analysed by using various cleavage agents (heparinases I and II, heparitinase/chondroitinases ABC and AC/periodate oxidation) followed by size-exclusion and anion-exchange HPLC. No modification was detected in the structure of the heparan sulphate chains. In contrast, the cytokine induced changes in the microcomposition of chondroitin/dermatan sulphate chains. More precisely, we found a decrease in the iduronic acid content, associated with down-regulation of the 4-O-sulphation on the GalNAc residues. In contrast, the 6-O-sulphation on these GalNAc residues was potentiated by the cytokine. These results indicate that IFNγ is able to modulate not only collagen but also the structure of galactosaminoglycans synthesized by human skin fibroblasts.