Mitogenic activity of S100A9 (MRP-14).

S100A9 is a calcium binding protein found in high amounts in granulocytes and monocytes. We have shown that S100A9 stimulated the proliferation of fibroblasts, but its mechanism remains unknown. In this report, S100A9 is shown to be mitogenic and to stimulate fibroblast proliferation without other growth factors in the serum. Although an S100A8/S100A9 heteropolymer inhibited the growth of fibroblasts by chelating zinc ions, these ions had no effect on the growth-stimulating activity of S100A9. The effects of serum and S100A9 on fibroblast growth were additive, and S100A9 stimulated the growth without serum. Furthermore, S100A9 stimulated the incorporation of bromodeoxyuridine in fibroblasts. However, the effect of S100A9 on the activation of extracellular signal regulated protein kinases (ERK) was small. These results suggest that S100A9 is involved in the regulation of inflammatory processes by modulating fibroblast proliferation.