Endothelin-1 enhances the proliferation of normal human melanocytes in a paradoxical manner from the TNF-α-inhibited condition, but tacrolimus promotes exclusively the cellular migration without proliferation: a proposed action mechanism for combination therapy of phototherapy and topical tacrolimus in vitiligo treatment.

摘要: Background  Vitiligo is an acquired pigmentary disorder caused by the destruction of melanocytes. Two major theories regarding pathogenesis vitiligo are autoimmune theory and autocytotoxicity theory, but, precise pathogenetic mechanism still not clarified. Objectives  We investigated effects ET-1, tacrolimus tumour necrosis factor-α (TNF-α) on proliferation migration cultured normal human melanocytes (NHMs). also sought to clarify theoretical rationale underlying topical monotherapy or tacrolimus-UV combination therapy as tools for treatment. Methods  The TNF-α proliferation/migration NHMs were MTT assay/Boyden chamber transwell assay. examined roles CXC-chemokine receptor II (CXCR II) matrix metalloproteinases (MMPs) in such conditions. Results  ET-1 exerted a stimulatory effect melanocyte migration, only higher than ET-1. inhibited dose-dependent manner. Paradoxically, TNF-α-pretreated exhibited enhanced proliferative efficiency after being switched found CXCRII was highly expressed TNF-α-incubated agents-free control, treatment preincubation showed levels expression condition incubated with alone. Moreover, greater activities MMP-2 MMP-9 induced reflected would enhance NHMs. Conclusions  Topical can be used effective agent monotherapy, maybe due its action inhibitory property, component UV treatment, considering more upregulated MMPs migrations feasible itself