Role of interleukin‐6 and endothelin‐1 receptors in enhanced melanocyte dendricity of facial spots and suppression of their ligands by niacinamide and tranexamic acid

黑素细胞 烟酰胺 色素沉着 医学 黑素体 角质形成细胞 氨甲环酸 黄褐斑 黑色素 受体 黑色素瘤 生物 皮肤病科 内科学 细胞培养 癌症研究 生物化学 外科 失血 遗传学 烟酰胺
作者
Tomohiro Hakozaki,J. Wang,T. Laughlin,Bradley B. Jarrold,Weiren Zhao,Masutaka Furue
出处
期刊:Journal of The European Academy of Dermatology and Venereology [Wiley]
卷期号:38 (S2): 3-10 被引量:5
标识
DOI:10.1111/jdv.19719
摘要

Hyperpigmented spots are common issues in all ethnicities with a hallmark characteristic of increased melanocyte dendricity.To determine (1) potential receptors and/or cytokines that are involved in increased melanocyte dendricity in multiple facial spot types; (2) treatment effects of skin-lightening compounds on identified cytokine release from keratinocytes and on dendricity in melanocytes.Facial spots (melasma, solar lentigo, acne-induced post-inflammatory hyperpigmentation) and adjacent non-spot skin biopsies were collected from Chinese women (age 20-70). The epidermal supra and basal layers were laser dissected to enrich keratinocyte or melanocyte biology respectively for transcriptome analysis. Melanocyte dendricity was assessed histologically by immunofluorescent staining. Effect of interleukin-6 (IL-6) and endothelin-1 (ET-1) on melanocyte dendricity and melanosome transfer were assessed in human melanocytes or melanocyte-keratinocyte co-culture models. Treatment effects of skin-lightening compounds (niacinamide, tranexamic acid [TxA], sucrose laurate/dilaurate mixture [SDL]) were assessed on IL-6 or ET-1 release from keratinocytes and on dendricity in melanocytes.Transcriptome analysis revealed IL-6 receptor and ET-1 receptor were significantly upregulated compared to the adjacent normal skin, visually confirmed at the protein level through immunostaining. Melanocytes in spot areas are more dendritic than melanocytes in adjacent non-spot skin. The addition of IL-6 and ET-1 to cell culture models increased melanocyte dendricity and melanosome transfer. IL-6 release was significantly suppressed by niacinamide and its combination, while ET-1 release was significantly reduced by both niacinamide and TxA. In contrast, SDL acted directly upon melanocytes to reduce dendricity.Interleukin-6 and ET-1 receptors are significantly upregulated in multiple facial spot types. The in vitro testing demonstrated their respective ligands increased melanocyte dendricity. Tested skin-lightening compounds showed reduction in release of IL-6/ET-1 from epidermal keratinocytes and/or inhibition of melanocyte dendricity. This work sheds light on pathophysiological mechanism of facial spots and potential new mechanisms of these skin-lightening compounds which warrant further human clinical validation.
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