title: UV-B radiation induces macrophage migration inhibitory factor-mediated melanogenesis through activation of protease-activated receptor-2 and stem cell factor in keratinocytes.
abstract: 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.
authors.affiliation: Department of Medical Information, Hokkaido Information University, Ebetsu, Japan.
authors.forename: Akiko
authors.initials: A
authors.lastname: Enomoto
authors.forename: Yoko
authors.initials: Y
authors.lastname: Yoshihisa
authors.forename: Takako
authors.initials: T
authors.lastname: Yamakoshi
authors.forename: Mati
authors.initials: M
authors.lastname: Ur Rehman
authors.forename: Osamu
authors.initials: O
authors.lastname: Norisugi
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Hara
authors.forename: Kenji
authors.initials: K
authors.lastname: Matsunaga
authors.forename: Teruhiko
authors.initials: T
authors.lastname: Makino
authors.forename: Jun
authors.initials: J
authors.lastname: Nishihira
authors.forename: Tadamichi
authors.initials: T
authors.lastname: Shimizu
mesh_terms: D000818:Animals; D002470:Cell Survival / Q000187:drug effects / Q000528:radiation effects; D002478:Cells, Cultured; D004817:Epidermis / Q000187:drug effects / Q000378:metabolism / Q000528:radiation effects; D006801:Humans; D015603:Keratinocytes / Q000187:drug effects / Q000378:metabolism* / Q000473:pathology / Q000528:radiation effects; D008263:Macrophage Migration-Inhibitory Factors / Q000494:pharmacology*; D008543:Melanins / Q000096:biosynthesis*; D008544:Melanocytes / Q000187:drug effects / Q000201:enzymology / Q000473:pathology / Q000528:radiation effects; D051379:Mice; D008822:Mice, Transgenic; D008954:Models, Biological; D014442:Monophenol Monooxygenase / Q000378:metabolism; D044464:Receptor, PAR-2 / Q000378:metabolism*; D012880:Skin Pigmentation / Q000187:drug effects / Q000528:radiation effects; D019089:Stem Cell Factor / Q000378:metabolism*; D013997:Time Factors; D046509:Tissue Culture Techniques; D014466:Ultraviolet Rays
chemical_list: D008263:Macrophage Migration-Inhibitory Factors; D008543:Melanins; D044464:Receptor, PAR-2; D019089:Stem Cell Factor; D014442:Monophenol Monooxygenase