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 collage n accumulation, there is biochemical and histologic evidence of elasti c tissue. Previous studies showed that glucocorticoid regulation of co llagen synthesis differs in fibroblasts from normal adult dermis and k eloids. To define further the abnormal regulation of matrix synthesis in keloid fibroblasts, we examined glucocorticoid regulation of elasti n synthesis. The basal level of elastin synthesis was significantly hi gher in keloid than in normal cells, and hydrocortisone reduced synthe sis of elastin and elastin mRNA in normal but not in keloid fibroblast s. We had shown previously that fibroblasts from fetal dermis resemble d keloid fibroblasts in glucocorticoid regulation of growth and collag en synthesis. In this study, glucocorticoids failed to down-regulate e lastin synthesis in fetal cells that had not differentiated to produce normal levels of elastin, whereas fetal cells with normal elastin pro duction exhibited glucocorticoid down-regulation. Abnormal regulation in keloid cells was independent of cell density and was confined to fi broblasts cultured from the keloid nodule. These findings reinforce th e conclusion that a matrix-regulatory pathway is deranged in these foc al lesions. Coordinate down-regulation of collagen and elastin by hydr ocortisone in normal adult dermal fibroblasts and the failure of hydro cortisone to down-regulate synthesis of either protein in keloid cells support the existence of common elements in the regulatory pathways o f these two matrix proteins.