PMID- 33517195
OWN - NLM
STAT- MEDLINE
DCOM- 20220113
LR  - 20220113
IS  - 1096-0023 (Electronic)
IS  - 1043-4666 (Linking)
VI  - 140
DP  - 2021 Apr
TI  - Tumor Necrosis Factor-alpha affects melanocyte survival and melanin synthesis via 
      multiple pathways in vitiligo.
PG  - 155432
LID - S1043-4666(21)00012-0 [pii]
LID - 10.1016/j.cyto.2021.155432 [doi]
AB  - Tumor necrosis factor-alpha (TNF-alpha) 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-alpha in melanocyte biology, 
      analyzing candidate molecules of melanocytes and immune homeostasis. Our results 
      showed increased TNF-alpha transcripts in vitiligenous lesional and non-lesional 
      skin. Melanocytes upon exogenous stimulation with TNF-alpha 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-alpha 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-alpha in melanocyte homeostasis and autoimmune 
      vitiligo pathogenesis.
CI  - Copyright (c) 2021 Elsevier Ltd. All rights reserved.
FAU - Singh, Mala
AU  - Singh M
AD  - Department of Biochemistry, Faculty of Science, The Maharaja Sayajirao University 
      of Baroda, Vadodara 390 002, Gujarat, India.
FAU - Mansuri, Mohmmad Shoab
AU  - Mansuri MS
AD  - Department of Biochemistry, Faculty of Science, The Maharaja Sayajirao University 
      of Baroda, Vadodara 390 002, Gujarat, India.
FAU - Kadam, Ashlesha
AU  - Kadam A
AD  - Department of Biochemistry, Faculty of Science, The Maharaja Sayajirao University 
      of Baroda, Vadodara 390 002, Gujarat, India.
FAU - Palit, Sayantani P
AU  - Palit SP
AD  - Department of Biochemistry, Faculty of Science, The Maharaja Sayajirao University 
      of Baroda, Vadodara 390 002, Gujarat, India.
FAU - Dwivedi, Mitesh
AU  - Dwivedi M
AD  - Department of Biochemistry, Faculty of Science, The Maharaja Sayajirao University 
      of Baroda, Vadodara 390 002, Gujarat, India.
FAU - Laddha, Naresh C
AU  - Laddha NC
AD  - Department of Biochemistry, Faculty of Science, The Maharaja Sayajirao University 
      of Baroda, Vadodara 390 002, Gujarat, India.
FAU - Begum, Rasheedunnisa
AU  - Begum R
AD  - Department of Biochemistry, Faculty of Science, The Maharaja Sayajirao University 
      of Baroda, Vadodara 390 002, Gujarat, India. Electronic address: 
      rasheedunnisab@yahoo.co.in.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20210128
PL  - England
TA  - Cytokine
JT  - Cytokine
JID - 9005353
RN  - 0 (Autophagy-Related Protein 12)
RN  - 0 (Beclin-1)
RN  - 0 (Interleukin-6)
RN  - 0 (Melanins)
RN  - 0 (Receptors, Tumor Necrosis Factor, Type I)
RN  - 0 (Receptors, Tumor Necrosis Factor, Type II)
RN  - 0 (Tumor Necrosis Factor-alpha)
RN  - 126547-89-5 (Intercellular Adhesion Molecule-1)
SB  - IM
MH  - Apoptosis/physiology
MH  - Autophagy-Related Protein 12/metabolism
MH  - Beclin-1/metabolism
MH  - Down-Regulation/physiology
MH  - Humans
MH  - Intercellular Adhesion Molecule-1/metabolism
MH  - Interleukin-6/metabolism
MH  - Melanins/*metabolism
MH  - Melanocytes/*metabolism
MH  - Receptors, Tumor Necrosis Factor, Type I/metabolism
MH  - Receptors, Tumor Necrosis Factor, Type II/metabolism
MH  - Signal Transduction/*physiology
MH  - Skin/metabolism
MH  - Tumor Necrosis Factor-alpha/*metabolism
MH  - Up-Regulation/physiology
MH  - Vitiligo/*metabolism
OTO - NOTNLM
OT  - Autoimmunity
OT  - Cytokine
OT  - Melanocyte
OT  - TNF-alpha
OT  - Vitiligo
EDAT- 2021/02/01 06:00
MHDA- 2022/01/14 06:00
CRDT- 2021/01/31 20:34
PHST- 2020/07/22 00:00 [received]
PHST- 2020/12/16 00:00 [revised]
PHST- 2020/12/17 00:00 [accepted]
PHST- 2021/02/01 06:00 [pubmed]
PHST- 2022/01/14 06:00 [medline]
PHST- 2021/01/31 20:34 [entrez]
AID - S1043-4666(21)00012-0 [pii]
AID - 10.1016/j.cyto.2021.155432 [doi]
PST - ppublish
SO  - Cytokine. 2021 Apr;140:155432. doi: 10.1016/j.cyto.2021.155432. Epub 2021 Jan 28.