Endothelin-1 of keratinocyte origin is a mediator of melanocyte dendricity.
Melanocytes synthesize melanin and transfer it to keratinocytes via dendritic processes. Keratinocytes are known to produce constitutively several factors, including endothelin-1 (ET-1), that together affect melanocyte proliferation, migration, melanogenesis, and dendrite formation. After ultraviolet (UV) irradiation, synthesis and secretion of ET-1 are up-regulated in keratinocytes. Because UV irradiation of skin is known to be associated with increased melanocyte dendricity, and because medium conditioned by UV-irradiated keratinocytes (UV-KCM) induces melanocyte dendricity to a greater degree than does baseline keratinocyte-conditioned medium (KCM), we investigated whether ET-1 promotes melanocyte dendricity. ET-1, originally recognized as a vasoconstrictive peptide, has recently been shown to stimulate melanocyte proliferation and tyrosinase activity. We now report that ET-1 supplementation of cultured melanocytes significantly increases the percentage of dendritic melanocytes, as well as dendrite length, in a dose-dependent manner. Moreover, UV-KCM was found to contain over 25-fold more ET-1 than KCM, and ET-1 supplementation of KCM induced melanocyte dendricity comparable to that induced by UV-KCM. Further, melanocyte dendricity induced by UV-KCM was significantly inhibited by the addition of anti-ET-1 monoclonal antibody to the medium, suggesting that the UV-KCM effect on melanocyte dendricity is mediated largely through ET-1. Our findings suggest that in the skin, ET-1 of keratinocyte origin promotes melanocyte dendricity in response to UV irradiation.
D002478:Cells, Cultured; D017077:Culture Media, Conditioned; D003712:Dendrites / Q000187:drug effects* / Q000502:physiology; D004305:Dose-Response Relationship, Drug; D016232:Endothelins / Q000378:metabolism / Q000494:pharmacology*; D006801:Humans; D015603:Keratinocytes / Q000502:physiology* / Q000528:radiation effects; D008544:Melanocytes / Q000166:cytology / Q000187:drug effects*; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology
D017077:Culture Media, Conditioned; D016232:Endothelins; D013755:Tetradecanoylphorbol Acetate