UV-B Radiation Induces Macrophage Migration Inhibitory Factor–Mediated Melanogenesis through Activation of Protease-Activated Receptor-2 and Stem Cell Factor in Keratinocytes

Department of Medical Information, Hokkaido Information University, Ebetsu, Japan.
American Journal Of Pathology (Impact Factor: 4.59). 02/2011; 178(2):679-87. DOI: 10.1016/j.ajpath.2010.10.021
Source: PubMed


UV radiation indirectly regulates melanogenesis in melanocytes through a paracrine regulatory mechanism involving keratinocytes. Protease-activated receptor (PAR)-2 activation induces melanosome transfer by increasing phagocytosis of melanosomes by keratinocytes. This study demonstrated that macrophage migration inhibitory factor (MIF) stimulated PAR-2 expression in human keratinocytes. In addition, we showed that MIF stimulated stem cell factor (SCF) release in keratinocytes; however, MIF had no effect on the release of endothelin-1 or prostaglandin E2 in keratinocytes. In addition, MIF had no direct effect on melanin and tyrosinase synthesis in cultured human melanocytes. The effect of MIF on melanogenesis was also examined using a three-dimensional reconstituted human epidermal culture model, which is a novel, commercially available, cultured human epidermis containing functional melanocytes. Migration inhibitory factor induced an increase in melanin content in the epidermis after a 9-day culture period. Moreover, melanin synthesis induced by UV-B stimulation was significantly down-regulated by anti-MIF antibody treatment. An in vivo study showed that the back skin of MIF transgenic mice had a higher melanin content than that of wild-type mice after 12 weeks of UV-B exposure. Therefore, MIF-mediated melanogenesis occurs mainly through the activation of PAR-2 and SCF expression in keratinocytes after exposure to UV-B radiation.

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Available from: Teruhiko Makino, Aug 02, 2014
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    • "Recently, it was demonstrated that the back skin of MIF transgenic (Tg) mice had a higher melanin content than that of wild-type (WT) mice after 12 weeks of UVB exposure. MIF mediated melanogenesis occurs mainly through the activation of protease-activated receptor-2 and stem cell factor expression in keratinocytes after exposure to UVB radiation (Enomoto et al., 2011). It has also been reported that MIF-deficient macrophages suppress the enhanced apoptosis and have restored proinflammatory function. "
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