BIPHASIC EFFECTS OF INTERLEUKIN-1-ALPHA ON DERMAL FIBROBLASTS - ENHANCEMENT OF CHEMOTACTIC RESPONSIVENESS AT LOW CONCENTRATIONS AND OF MESSENGER-RNA EXPRESSION FOR COLLAGENASE AT HIGH-CONCENTRATIONS

Fibrotic reactions in the skin are frequently preceded by infiltration of inflammatory cells and subsequent migration of fibroblastic cells. Interleukin-1 is secreted by inflammatory cells and can regulate proliferation and protein synthesis of fibroblasts. its role in fibroblast chemotaxis has not been elucidated in any detail. Using the well-established Boyden chamber assay for measurement of chemotaxis in vitro, we studied a wide range of recombinant human interleukin-1alpha concentrations to assess intrinsic chemotactic activity of interleukin-1alpha and to determine the capacity of this mediator to modify the chemotactic response of fibroblasts to other chemoattractants. This was compared with the interleukin-1alpha dose required for enhancement of mRNA expression for collagenase. Although interleukin-1alpha was not chemoattractive for fibroblasts, it specifically augmented migration toward fibroblast-conditioned medium and toward platelet-derived growth factor but not toward epidermal growth factor, fibronectin, or transforming-growth factor-beta. Interleukin-1alpha did not measurably alter the expression of mRNA for the platelet-derived growth factor receptor or its platelet-derived growth factor-binding characteristics. Doses required to enhance fibroblast chemotaxis were distinctly lower than those required for stimulation of collagenase mRNA expression.