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

Abstract

Topical tacrolimus can be used an effective agent for vitiligo treatment as monotherapy, maybe due to its migration stimulatory action or TNF-α 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-1.

Inhibition of melanogenesis by Gaillardia aristata flower extract

“…The mechanism of epidermal hyper-pigmentation occurs by the increased expression level of ET-1 and SCF, or the decreased expression of TNF-α and IL-6. In particular, SCF and ET-1 are germane to the hyper-pigmentary mechanism by UVB-induced melanin synthesis [26][27][28][29][30]. Presently, GAE inhibited SCF-stimulated pigmentation in human epidermal equivalents.…”

Narrowband ultraviolet B phototherapy in combination with other therapies for vitiligo: mechanisms and efficacies

“…TCIs are presumed to induce repigmentation by modulating the immune response as well as by targeting melanocytes and melanocyte reservoirs. Tacrolimus may suppress levels of tumour necrosis factor‐alpha (TNF‐α), a pro‐inflammatory cytokine which is higher in vitiliginous lesions and is also known to suppress melanin production . Tacrolimus may also stimulate melanocyte proliferation (via stem cell factor, which is lower in vitiliginous lesions), migration (via MMP‐9) and melanin synthesis …”

FK506 positively regulates the migratory potential of melanocyte‐derived cells by enhancing syndecan‐2 expression

“…Here, we show that FK506 promotes migration at least in part by regulating syndecan‐2 expression in melanocytes and melanoma cells. Previous reports showed that FK506 regulates melanocyte migration by increasing MMP activity (Lee et al., ) and promoting the secretion of cytokines from keratinocytes (Lan et al., ). As also found in these prior reports, we observed that FK506 treatment increased cell migration and wound healing in melanoma cells and melanocytes (Figure and ).…”

“…In addition, Lee et al. () reported that FK506 promotes the activities of MMP‐2 and MMP‐9 and that cotreatment of melanocytes with FK506 plus endothelin (which is secreted by keratinocytes in response to UV) induces migration more effectively than monotreatment. However, the mechanism through which FK506 regulates cell migration remains unclear.…”