Biphasic effects of interleukin-1 alpha on dermal fibroblasts: enhancement of chemotactic responsiveness at low concentrations and of mRNA expression for collagenase at high concentrations

Abstract

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-1 alpha concentrations to assess intrinsic chemotactic activity of interleukin-1 alpha and to determine the capacity of this mediator to modify the chemotactic response of fibroblasts to other chemoattractants. This was compared with the interleukin-1 alpha dose required for enhancement of mRNA expression for collagenase. Although interleukin-1 alpha 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-1 alpha 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.