Expression and function of neurotrophins and their receptors in human melanocytes

Synopsis Melanocytes and cells of the nervous system are of common ectodermal origin and neurotrophins (NT) have been shown to be released by human keratinocytes. We investigated the expression and function of NT [nerve growth factor (NGF), brain-derived neurotrophic factor (BDNF), NT-3, NT-4/-5] and their receptors in human melanocytes. Human melanocytes produce all NT in different amounts, whereas they only release NT-4. NT-4 release is downregulated, whereas NT-3 is upregulated by ultraviolet (UVB) irradiation. Melanocytes treated with phorbol 12-myristate 13-acetate (PMA) express TrkA and TrkB, but not TrkC. NT fail to stimulate melanocyte proliferation, whereas they stimulate the synthesis of tyrosinase and tyrosinase-related protein-1 (TRP-1). Finally, NT-3, NT-4 and NGF increase melanin production. Taken together, these results demonstrate an intriguing interaction between melanocytes and the nervous system. We speculate that NT could be considered the target of therapy for disorders of skin pigmentation. Resume Les melanocytes et le systeme nerveux central ont en commun une origine ectodermique et les neurotrophines (NT) sont connues pour etre liberees par les keratinocytes. Dans la presente etude nous decrivons l'expression, la fonction des neurotrophines et leurs recepteurs chez les melanocytes humains normaux. Les melanocytes produisent toutes les NT en differentes quantites, mais ne liberent que la NT-4. L'irradiation UVB decroit la production de NT-4 et stimule celle de NT-3. Les melanocytes traites au PMA expriment TrkA et TrkB mais pas TrkC. Les Neurotrophines stimulent pas la proliferation des melanocytes mais stimulent la synthese de la tyrosinase et de la TRP-1. Finallement, NT-3, NT-4 et le NGF augmentent la production de melanine. L ’ensemble de ces resultats demontrent une interaction entre le systeme nerveux et les melanocytes. Nous emettons l'hypothese que les NT doivent etre considerees comme des cibles serieuses pour la correction des desordres de pigmentation cutanee.