Tumor Necrosis Factor-alpha affects melanocyte survival and melanin synthesis via multiple pathways in vitiligo.
Cytokine
; 140: 155432, 2021 04.
Article
em En
| MEDLINE
| ID: mdl-33517195
ABSTRACT
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.
Palavras-chave
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Vitiligo
/
Transdução de Sinais
/
Fator de Necrose Tumoral alfa
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Melaninas
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Melanócitos
Limite:
Humans
Idioma:
En
Revista:
Cytokine
Assunto da revista:
ALERGIA E IMUNOLOGIA
Ano de publicação:
2021
Tipo de documento:
Article
País de afiliação:
Índia