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Alpha-thrombin stimulates expression of macrophage migration inhibitory factor in skin fibroblasts
T Shimizu1, A Ohkawara, Y Mizue
1Department of Dermatology, Hokkaido University School of Medicine, Sapporo, Japan.
Abstract:
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.
Insights
Alpha-thrombin significantly boosts macrophage migration inhibitory factor (MIF) production in skin fibroblasts. This suggests MIF plays a key role in wound repair by regulating inflammatory responses during healing.
Area of Science:
- Biochemistry
- Immunology
- Dermatology
Background:
- Macrophage migration inhibitory factor (MIF) is crucial for inflammatory and immunological responses, often induced by wounds and infections.
- Increased MIF expression is observed during the wound healing process in rat skin, with enhanced presence in lesions.
- Alpha-thrombin, a serine protease, is known to influence wound healing by inducing inflammatory cytokines like IL-6.
Purpose of the Study:
- To investigate the effect of alpha-thrombin on MIF production in human skin fibroblasts.
- To understand the role of fibroblast-derived MIF in the context of wound repair.
Main Methods:
- Enzyme-linked immunosorbent assay (ELISA) to quantify MIF secretion into fibroblast culture medium.
- Northern blot analysis to assess MIF mRNA upregulation in response to alpha-thrombin.
Main Results:
- Alpha-thrombin significantly stimulated MIF secretion from human skin fibroblasts.
- Northern blot analysis confirmed the upregulation of MIF mRNA following alpha-thrombin treatment.
- Immunohistochemical analysis showed enhanced MIF expression in rat wound skin lesions.
Conclusions:
- Fibroblasts produce MIF in response to alpha-thrombin.
- This alpha-thrombin-induced MIF production by fibroblasts is suggested to play a significant regulatory role in wound repair processes.