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Expression and function of neurotrophins and their receptors in human melanocytes

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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.

French
Résumé

Les melanocytes et le système nerveux central ont en commun une origine ectodermique et les neurotrophines (NT) sont connues pour etre libérées par les kératinocytes. Dans la présente étude nous décrivons l'expression, la fonction des neurotrophines et leurs récepteurs chez les mélanocytes humains normaux. Les mélanocytes produisent toutes les NT en différentes quantités, mais ne libèrent que la NT-4. L'irradiation UVB decroit la production de NT-4 et stimule celle de NT-3. Les mélanocytes traités au PMA expriment TrkA et TrkB mais pas TrkC. Les Neurotrophines stimulent pas la prolifération des mélanocytes mais stimulent la synthèse de la tyrosinase et de la TRP-1. Finallement, NT-3, NT-4 et le NGF augmentent la production de mélanine. L ’ensemble de ces résultats démontrent une interaction entre le système nerveux et les mélanocytes. Nous émettons l'hypothèse que les NT doivent etre considérées comme des cibles sérieuses pour la correction des désordres de pigmentation cutanée.
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Keywords: melanocyte; melanogenesis; neurotrophin receptor; ultraviolet radiation

Document Type: Research Article

Affiliations: 1: Institute of Dermatology and Plastic Surgery Unit, University of Modena and Reggio Emilia, 41100 Modena, Italy 2: LVMH Recherche, 45804 Saint Jean de Braye, France

Publication date: August 1, 2006

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