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, MIFmediated melanogenesis occurs mainly through the activation of PAR-2 and SCF expression in keratino- Exposure to UV radiation leads to various short-term deleterious cutaneous effects, including sunburn and immunosuppression, and long-term consequences that lead to premature aging, including hyperpigmentation.1 UV radiation indirectly regulates melanogenesis in melanocytes through a paracrine regulatory mechanism involving keratinocytes. UV-B-induced pigmentation occurs when human keratinocytes exposed to UV-B are stimulated to produce and secrete several mediators that trigger the activation of melanocytes and act as potent mitogens and melanogens for human melanocytes.2-4 The two main paracrine melanogenic cytokines, stem cell factor (SCF) and endothelin (ET)-1, have been demonstrated to play pivotal roles in skin pigmentation, including UV-Binduced pigmentation. 5 In addition, prostaglandins (PGs) are key mediators of diverse functions in the skin; and several reports 6,7 have suggested that PGs mediate postinflammatory pigmentary changes by modulating melanin synthesis and melanocyte dendricity.Protease-activated receptor (PAR)-2 is a member of a novel G-protein-coupled seven-transmembrane receptor family.8 These receptors are irreversibly activated through proteolytic cleavage of their amino termini. Subsequent to proteolytic cleavage, the newly exposed NH2 terminus acts as a tethered peptide ligand, which binds and activates the receptor. Protease-activated receptor-2 is involved in skin pigmentation because it increases the phagocytosis of melanosomes by keratinocytes.9 UV ir-
Lichen amyloidosis (LA) is a type of primary localized cutaneous amyloidosis characterized by multiple pruritic discrete hyperkeratotic papules with amyloid deposition in the papillary dermis. Two patients with LA had been treated with topical corticosteroids, but with no effect on the eruptions. The present authors then started treating the affected area by superficial ablation using a CO2 surgical laser (LASER 30C, Lumenis Inc., Yokneum, Israel) at a setting of 10-15 watts with a 0.12-second pulse duration, 0.36-second rest duration, and 5-mm laser spot size. The present authors treated the patients twice a month with the CO2 laser. The papules on the legs had flattened in both patients, with a great improvement in the severe itching after 6 months in Case 1 and after 10 months in Case 2. These cases indicate that the CO2 laser led to a good response in terms of the clinical manifestations, and may be useful for the treatment of LA.
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