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- Title
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.
- Authors
Hakozaki, T.; Wang, J.; Laughlin, T.; Jarrold, B.; Zhao, W.; Furue, M.
- Abstract
Background: Hyperpigmented spots are common issues in all ethnicities with a hallmark characteristic of increased melanocyte dendricity. Objectives: 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. Methods: 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. Results: 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. Conclusion: 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.
- Subjects
INTERLEUKIN-6 receptors; TRANEXAMIC acid; HYPERPIGMENTATION; NICOTINAMIDE; MICROPHTHALMIA-associated transcription factor; LIGANDS (Biochemistry); CHINESE people
- Publication
Journal of the European Academy of Dermatology & Venereology, 2024, Vol 38, p3
- ISSN
0926-9959
- Publication type
Article
- DOI
10.1111/jdv.19719