Effect of Glucocorticoids on Glycosaminoglycan Metabolism in Cultured Human Skin Fibroblasts

Human skin fibroblasts were exposed to 3 anti-inflammatory steroids in order to study their effects on the glycosaminoglycan metabolism. The potent glucocorticoids, fluocinolone acetonide and budesonide, even at low concentrations strongly reduced the accumulation of hyaluronic acid and sulfated glycosaminoglycans in the medium, at the cell surface, and in the cells. Hydrocortisone had considerably less effect. The 3 compartments were not influenced to the same extent and the least inhibition was noted in the cell surface pool. Dermatan sulfate was decreased to the same relative extent in all 3 compartments, while hyaluronic acid and heparan sulfate were specifically retained at the cell surface, explaining why this compartment was less affected than the others.Dermatan sulfate was studied in more detail regarding effects on its copolymeric structure. Glucocorticoid treatment changed the uronosyl composition of the polysaccharides so that a relative decrease of glucuronic acid residues and a relative increase of iduronic acid residues were noted. This change was most evident in dermatan sulfate of the medium and of the cell surface.Thus, glucocorticoid treatment not only reduces the quantity of various glycosaminoglycans but also changes the distribution, the relative proportion, and the structure of connective tissue proteoglycans. These effects probably contribute to the development of skin atrophy, which often is observed after long-term treatment with potent glucocorticoids