Poster presentation, P37

Official XXIst International Pigment Cell Conference website - 21-24 Sept 2011, Bordeaux - France | updated: September 04 2011

Melanogenesis mediated by the preservative-induced release of the macrophage migration inhibitory factor in a 3D epidermal model

SPEAKER S. Ishiwatari #whois submiter ?
AUTHOR(s) S. Ishiwatari, T. Fujita, A. Enomoto, S. Matsukuma

Melanogenesis in the skin is stimulated in response to various environmental factors such as UV radiation, environmental pollutants, and chemical compounds. Among these factors, our focus is on agents that are absorbed into the skin through daily topical application. We previously reported that certain preservatives increased the melanin content in a reconstituted 3D human epidermal model (MelanoDermTM). In this study, to investigate the possible mechanism by which such preservatives enhance melanin synthesis, we examined the effects of methyl lparaben (MP) on the protein profile in a 3D epidermal model by performing 2D electrophoresis 12 days after MP exposure. The results revealed that approximately 31 proteins probably underwent changes due to MP exposure. These candidate proteins and proteins, which are reported to have an association with melanogenesis, in normal human keratinocytes (NHEKs), normal human melanocytes (NHEMs), and a 3D epidermal model were analyzed by ELISA or immunoblotting after MP exposure. One of the markedly altered proteins was macrophage migration inhibitory factor (MIF). MIF secretion into the culture medium increased notably in the NHEKs, NHEMs, and 3D epidermal model after MP exposure. According to a recent study, MIF mediates melanogenesis mainly by activating protease-activated receptor-2 (PAR-2) in keratinocytes following exposure to UVB radiation. PAR-2 is a key regulatory factor in keratinocytes, as it mediates melanosome transfer. Therefore, PAR-2 expression in keratinocytes was analyzed after MP exposure, and it was observed that MP enhanced PAR-2 expression in keratinocytes. Furthermore, induction of tyrosinase and tyrosinase-related protein 1 was confirmed in the NHEMs and 3D epidermal model. These data suggest that MP affects both keratinocytes and melanocytes and may stimulate melanogenesis via the MIF pathway.



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