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Updated: Jun 4, 2026

Pharmacologic Induction of Epidermal Melanin and Protection Against Sunburn in a Humanized Mouse Model
Published on: September 7, 2013
UV-B radiation induces macrophage migration inhibitory factor-mediated melanogenesis through activation of
Akiko Enomoto1, Yoko Yoshihisa, Takako Yamakoshi
1Department of Medical Information, Hokkaido Information University, Ebetsu, Japan.
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.
Insights
Macrophage migration inhibitory factor (MIF) promotes skin pigmentation by stimulating keratinocytes. MIF enhances melanin production indirectly, primarily through Protease-activated receptor (PAR)-2 and stem cell factor (SCF) pathways after UV exposure.
Area of Science:
- Dermatology
- Cell Biology
- Molecular Biology
Background:
- UV radiation influences skin pigmentation via paracrine signaling between keratinocytes and melanocytes.
- Protease-activated receptor (PAR)-2 activation in keratinocytes promotes melanosome transfer, a key step in melanogenesis.
Purpose of the Study:
- To investigate the role of macrophage migration inhibitory factor (MIF) in UV-induced melanogenesis.
- To elucidate the mechanisms by which MIF regulates pigmentation in human skin models.
Main Methods:
- In vitro studies using cultured human keratinocytes and melanocytes.
- Three-dimensional reconstituted human epidermis models.
- In vivo studies using MIF transgenic mice and UV-B exposure.
Main Results:
- MIF stimulated PAR-2 and stem cell factor (SCF) expression in keratinocytes but not endothelin-1 or prostaglandin E2 release.
- MIF did not directly affect melanin or tyrosinase synthesis in melanocytes.
- MIF increased melanin content in a 3D skin model and in MIF transgenic mice after UV-B exposure.
- Anti-MIF antibody treatment reduced UV-B-induced melanin synthesis.
Conclusions:
- MIF plays a significant role in UV-B-induced melanogenesis.
- MIF-mediated pigmentation primarily occurs through PAR-2 and SCF activation in keratinocytes.
- MIF represents a potential therapeutic target for modulating skin pigmentation.
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