Serum growth factors and proinflammatory cytokines are potent inducers of activin expression in cultured fibroblasts and keratinocytes.

Recently we demonstrated a large induction of activin expression in fibroblasts and keratinocytes after cutaneous injury in mice. To identify possible mediators of activin induction during skin repair, we have now analyzed the regulation of this factor in cultured keratinocytes and fibroblasts. Here we show that activin A mRNA and protein levels are low in quiescent keratinocytes and fibroblasts but expression is strongly induced upon serum treatment. The stimulatory effect of serum on activin expression is likely to be a combinatorial effect of different growth factors, since platelet-poor plasma serum and several purified serum growth factors also stimulated activin expression, although to a lesser extent than complete serum. Furthermore, we found increased expression of activin in keratinocytes and fibroblasts after addition of the proinflammatory cytokines interleukin 1beta and tumor necrosis factor alpha. Taken together, our data suggest that serum growth factors which are released upon hemorrhage as well as proinflammatory cytokines derived from neutrophils and macrophages might be responsible for induction of activin expression after injury.