GLUCOCORTICOID REGULATION OF ELASTIN SYNTHESIS IN HUMAN FIBROBLASTS - DOWN-REGULATION IN FIBROBLASTS FROM NORMAL DERMIS BUT NOT FROM KELOIDS

Keloids arise as benign connective tissue masses at sites of injury in genetically predisposed individuals. In addition to excessive collagen accumulation, there is biochemical and histologic evidence of elastic tissue. Previous studies showed that glucocorticoid regulation of collagen synthesis differs in fibroblasts from normal adult dermis and keloids. To define further the abnormal regulation of matrix synthesis in keloid fibroblasts, we examined glucocorticoid regulation of elastin synthesis. The basal level of elastin synthesis was significantly higher in keloid than in normal cells, and hydrocortisone reduced synthesis of elastin and elastin mRNA in normal but not in keloid fibroblasts. We had shown previously that fibroblasts from fetal dermis resembled keloid fibroblasts in glucocorticoid regulation of growth and collagen synthesis. In this study, glucocorticoids failed to down-regulate elastin synthesis in fetal cells that had not differentiated to produce normal levels of elastin, whereas fetal cells with normal elastin production exhibited glucocorticoid down-regulation. Abnormal regulation in keloid cells was independent of cell density and was confined to fibroblasts cultured from the keloid nodule. These findings reinforce the conclusion that a matrix-regulatory pathway is deranged in these focal lesions. Coordinate down-regulation of collagen and elastin by hydrocortisone in normal adult dermal fibroblasts and the failure of hydrocortisone to down-regulate synthesis of either protein in keloid cells support the existence of common elements in the regulatory pathways of these two matrix proteins.