Alpha-thrombin stimulates expression of macrophage migration inhibitory factor in skin fibroblasts.

Macrophage migration inhibitory factor (MIF) is induced by various stimuli such as wounds and infection and regulates inflammatory and immunological responses. To date, we have found increased expression of MIF during the wound healing process in rat skin. Immunohistochemical analysis demonstrated enhanced expression of MIF in wound skin lesions. On the other hand, alpha-thrombin, a multifunctional serine protease, plays an important role in wound healing with regard to induction of inflammatory cytokines such as interleukin-6 (IL-6). Accordingly, we examined the effect of alpha-thrombin on MIF production in human skin fibroblasts. Alpha-thrombin significantly stimulated MIF secretion into culture medium of fibroblasts quantitated by an enzyme-linked immunosorbent assay (ELISA). Consistent with this, we observed the upregulation of MIF mRNA in response to alpha-thrombin by Northern blot analysis. Taken together, these results suggest that MIF produced by fibroblasts in response to alpha-thrombin plays an important regulatory role in wound repair.