STIMULATION OF SULFATED GLYCOSAMINOGLYCAN AND DECORIN PRODUCTION IN ADULT DERMAL FIBROBLASTS BY RECOMBINANT HUMAN INTERLEUKIN-4

Interleukin-4 (IL-4) is a pleiotropic cytokine expressed by inflammato ry cells. Previous work from our laboratory has shown that it stimulat es collagen synthesis in fibroblasts. Here we report the effects of re combinant human IL-4 on glycosaminoglycan (GAG) and proteoglycan synth esis in normal dermal fibroblasts from adult donors. IL-4 (10 and 100 units/ml) induced a dose-dependent increase of [H-3]glucosamine and [S -35]sulphate incorporation into total GAGs. The analysis of the differ ent GAG fractions indicated the enhanced synthesis of dermatan/chondro itin sulphates. IL-4 had no effect on hyaluronan synthesis. The increa se of sulphated GAG synthesis was correlated with an increase of prote oglycans in the culture medium. Decorin was identified as the major ch ondroitin/dermatan sulphate-containing proteoglycan in the culture med ium of fibroblasts. Its synthesis was strongly stimulated by IL-4. Bot h the core-protein synthesis and mRNA expression were enhanced, indica ting that the cytokine acted, at least in part, at the pre-translation al level. These results indicate that IL-4 is able to modulate not onl y collagen, but also proteoglycan, production by human fibroblasts. Th eir implications in physiopathological processes such as wound healing or fibrosis is suggested.