Cytokines alter mRNA steady state levels for basement membrane proteins in human skin fibroblasts.

Keratinocytes and fibroblasts synthesize basement membrane proteins and even contribute to the formation of basement membrane structures following injury or tissue damage. Under these conditions many cellular functions are regulated by mediators e.g. transforming growth factor-beta, tumor necrosis factor alpha, interferon-gamma or interleukin-1 alpha. We therefore describe here their influence on synthesis of basement membrane proteins in human skin fibroblasts. A comparative analysis of mRNA steady levels coding for BM-40, nidogen, laminin B1 and B2 chains and collagen IV in fibroblasts, in primary human keratinocytes and a epidermal cell line grown in monolayer culture demonstrated that the highest amounts were present in human fibroblasts. Interferon-gamma reduces all mRNA steady state levels dose dependently in comparison to the control, while transforming growth factor-beta simultaneously induces BM-40, alpha 1 and alpha 2 (IV) collagen mRNAs. TGF-beta, however, has no effect on nidogen and laminin mRNA levels. Interleukin-1 alpha and tumor necrosis factor alpha do not affect the mRNA levels of most basement membrane proteins. However, the alpha 1 (IV) collagen mRNA is upregulated by both cytokines to 300%. These data demonstrate a specific control of the expression of several basement membrane proteins by cytokines and indicate that fibroblasts could contribute to basement membrane formation during wound healing and tissue repair.