Fibroblasts from keloids, benign collagenous tumors that develop as a result of an inherited defect in dermal wound healing, respond abnormally to several effectors of wound healing. Hydrocortisone stimulates the growth of normal but not keloid fibroblasts and reduces both the rate of collagen synthesis and levels of collagen mRNA in normal but not keloid cells. Interferon (IFN) has also been reported to decrease the rate of collagen synthesis relative to total protein synthesis-in human fibroblasts. A possible mechanism for the differential effects of hydrocortisone on growth and collagen synthesis in keloid and normal cells is a differential production of or response to IFN. The goals of this project are: 1) to characterize the effects of IFN-alpha, beta and gamma on growth, collagen synthesis and collagen mRNA levels in normal and keloid cells; 2) to determine the effects of induced endogenous IFN on growth, collagen synthesis and collagen mRNA levels in normal and keloid cells and compare these effects to those produced by exogenous IFN. Poly(I) poly(C) will be used to induce IFN production in the fibroblasts: 3) to determine whether hydrocortisone modulates the effect of IFN on growth, collagen synthesis or collagen mRNA levels in normal and keloid cells; 4) to determine whether hydrocortisone modulates IFN mRNA level and/or 2'-5' oligoadenylate synthetase (OASE) activity in normal and keloid cells; 5) to determine whether phorbol esters modulate the effect of IFNs on growth, collagen synthesis, collagen mRNA levels, or OASE activity in normal and keloid cells. Results of these studies should help to determine whether IFN is an important mediator of the differential effects produced by hydrocortisone.
