{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,20]],"date-time":"2026-07-20T11:45:35Z","timestamp":1784547935518,"version":"3.55.0"},"reference-count":32,"publisher":"Wiley","issue":"5","license":[{"start":{"date-parts":[[2012,3,9]],"date-time":"2012-03-09T00:00:00Z","timestamp":1331251200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Acad Dermatol Venereol"],"published-print":{"date-parts":[[2013,5]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p><jats:bold>Background\u2002<\/jats:bold> Vitiligo is an acquired pigmentary disorder caused by the destruction of melanocytes. Two of the major theories regarding the pathogenesis of vitiligo are the autoimmune theory and autocytotoxicity theory, but, the precise pathogenetic mechanism is still not clarified.<\/jats:p><jats:p><jats:bold>Objectives\u2002<\/jats:bold> We investigated the effects of ET\u20101, tacrolimus and tumour necrosis factor\u2010\u03b1 (TNF\u2010\u03b1) on proliferation and migration of cultured normal human melanocytes (NHMs). We also sought to clarify the theoretical rationale underlying the topical tacrolimus monotherapy or tacrolimus\u2010UV combination therapy as tools for vitiligo treatment.<\/jats:p><jats:p><jats:bold>Methods\u2002<\/jats:bold> The effects of ET\u20101, tacrolimus and TNF\u2010\u03b1 on proliferation\/migration of cultured NHMs were investigated by MTT assay\/Boyden chamber transwell migration assay. We also examined roles of CXC\u2010chemokine receptor II (CXCR II) and matrix metalloproteinases (MMPs) in such conditions.<\/jats:p><jats:p><jats:bold>Results\u2002<\/jats:bold> ET\u20101 exerted a stimulatory effect on melanocyte proliferation and migration, but, tacrolimus exerted a stimulatory effect only on melanocyte migration higher than ET\u20101. TNF\u2010\u03b1 inhibited melanocyte proliferation in a dose\u2010dependent manner. Paradoxically, TNF\u2010\u03b1\u2010pretreated NHMs exhibited an enhanced proliferative efficiency after being switched to ET\u20101. We found CXCRII was highly expressed in TNF\u2010\u03b1\u2010incubated melanocytes than the agents\u2010free control, and ET\u20101 treatment after TNF\u2010\u03b1 preincubation showed the higher levels of CXCRII expression than the condition incubated with TNF\u2010\u03b1 alone. Moreover, the greater activities of MMP\u20102 and MMP\u20109 induced by tacrolimus than ET\u20101, reflected tacrolimus would enhance migration stimulatory effect in cultured NHMs.<\/jats:p><jats:p><jats:bold>Conclusions\u2002<\/jats:bold> Topical tacrolimus can be used an effective agent for vitiligo treatment as monotherapy, maybe due to its migration stimulatory action or TNF\u2010\u03b1 inhibitory property, and also as a component in combination therapy with UV treatment, considering the more upregulated MMPs activities are induced and the more effective migrations are feasible by itself than ET\u20101.<\/jats:p>","DOI":"10.1111\/j.1468-3083.2012.04498.x","type":"journal-article","created":{"date-parts":[[2012,3,9]],"date-time":"2012-03-09T12:29:29Z","timestamp":1331296169000},"page":"609-616","source":"Crossref","is-referenced-by-count":33,"title":["Endothelin\u20101 enhances the proliferation of normal human melanocytes in a paradoxical manner from the TNF\u2010\u03b1\u2010inhibited condition, but tacrolimus promotes exclusively the cellular migration without proliferation: a proposed action mechanism for combination therapy of phototherapy and topical tacrolimus in vitiligo 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