ENDOTHELIN-1 OF KERATINOCYTE ORIGIN IS A MEDIATOR OF MELANOCYTE DENDRICITY

Melanocytes synthesize melanin and transfer it to keratinocytes via de ndritic processes, Keratinocytes are known to produce constitutively s everal factors, including endothelin-1 (ET-1), that together affect me lanocyte proliferation, migration, melanogenesis, and dendrite formati on, 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 beca use medium conditioned by UV-irradiated keratinocytes (UV-KCM) induces melanocyte dendricity to a greater degree than does baseline keratino cyte-conditioned medium (KCM), we investigated whether ET-1 promotes m elanocyte dendricity, ET-1, originally recognized as a vasoconstrictiv e peptide, has recently been shown to stimulate melanocyte proliferati on and tyrosinase activity, We now report that ET-1 supplementation of cultured melanocytes significantly increases the percentage of dendri tic melanocytes, as well as dendrite length, in a dose-dependent manne r, Moreover, UV-KCM was found to contain over 25-fold more ET-1 than K CM, and ET-1 supplementation of KCM induced melanocyte dendricity comp arable to that induced by UV-KCM, Further, melanocyte dendricity induc ed by UV-KCM was significantly inhibited by the addition of anti-ET-1 monoclonal antibody to the medium, suggesting that the UV-KCM effect o n melanocyte dendricity is mediated largely through ET-1, Our findings suggest that in the skin, ET-1 of keratinocyte origin promotes melano cyte dendricity in response to UV irradiation.