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.