Tumor Necrosis Factor-alpha affects melanocyte survival and melanin synthesis via multiple pathways in vitiligo.

Autor: Singh M; Department of Biochemistry, Faculty of Science, The Maharaja Sayajirao University of Baroda, Vadodara 390 002, Gujarat, India., Mansuri MS; Department of Biochemistry, Faculty of Science, The Maharaja Sayajirao University of Baroda, Vadodara 390 002, Gujarat, India., Kadam A; Department of Biochemistry, Faculty of Science, The Maharaja Sayajirao University of Baroda, Vadodara 390 002, Gujarat, India., Palit SP; Department of Biochemistry, Faculty of Science, The Maharaja Sayajirao University of Baroda, Vadodara 390 002, Gujarat, India., Dwivedi M; Department of Biochemistry, Faculty of Science, The Maharaja Sayajirao University of Baroda, Vadodara 390 002, Gujarat, India., Laddha NC; Department of Biochemistry, Faculty of Science, The Maharaja Sayajirao University of Baroda, Vadodara 390 002, Gujarat, India., Begum R; Department of Biochemistry, Faculty of Science, The Maharaja Sayajirao University of Baroda, Vadodara 390 002, Gujarat, India. Electronic address: rasheedunnisab@yahoo.co.in.
Jazyk: angličtina
Zdroj: Cytokine [Cytokine] 2021 Apr; Vol. 140, pp. 155432. Date of Electronic Publication: 2021 Jan 28.
DOI: 10.1016/j.cyto.2021.155432
Abstrakt: Tumor necrosis factor-α (TNF-α) is a major mediator of inflammation and its increased levels have been analyzed in vitiligo patients. Vitiligo is a depigmentary skin disarray caused due to disapperance of functional melanocytes. The aim of the study was to investigate the role of TNF-α in melanocyte biology, analyzing candidate molecules of melanocytes and immune homeostasis. Our results showed increased TNF-α transcripts in vitiligenous lesional and non-lesional skin. Melanocytes upon exogenous stimulation with TNF-α exhibited a significant reduction in cell viability with elevated cellular and mitochondrial ROS and compromised complex I activity. Moreover, we observed a reduction in melanin content via shedding of dendrites, down-regulation of MITF-M, TYR and up-regulation of TNFR1, IL6, ICAM1 expression, whereas TNFR2 levels remain unaltered. TNF-α exposure stimulated cell apoptosis at 48 h and autophagy at 12 h, elevating ATG12 and BECN1 transcripts. Our novel findings establish the functional link between autophagy and melanocyte destruction. Overall, our study suggests a key function of TNF-α in melanocyte homeostasis and autoimmune vitiligo pathogenesis.
(Copyright © 2021 Elsevier Ltd. All rights reserved.)
Databáze: MEDLINE
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