PUBLICATION
IL-17 induces cellular stress microenvironment of melanocytes to promote autophagic cell apoptosis in vitiligo
- Authors
- Zhou, J., An, X., Dong, J., Wang, Y., Zhong, H., Duan, L., Ling, J., Ping, F., Shang, J.
- ID
- ZDB-PUB-180404-8
- Date
- 2018
- Source
- FASEB journal : official publication of the Federation of American Societies for Experimental Biology 32(9): 4899-4916 (Journal)
- Registered Authors
- Keywords
- autophagy, depigmentary disorder, interleukin-17, mitochondria, oxidative stress
- MeSH Terms
-
- Animals
- Apoptosis/drug effects*
- Apoptosis/physiology
- Autophagy/drug effects*
- Cells, Cultured
- Cellular Microenvironment/drug effects*
- Interleukin-17/metabolism
- Interleukin-17/pharmacology*
- Keratinocytes/pathology
- Male
- Melanocytes/drug effects*
- Melanocytes/pathology
- Mice, Inbred C57BL
- Oxidative Stress/drug effects
- Reactive Oxygen Species/metabolism
- Vitiligo/drug therapy*
- Vitiligo/metabolism
- PubMed
- 29613836 Full text @ FASEB J.
Citation
Zhou, J., An, X., Dong, J., Wang, Y., Zhong, H., Duan, L., Ling, J., Ping, F., Shang, J. (2018) IL-17 induces cellular stress microenvironment of melanocytes to promote autophagic cell apoptosis in vitiligo. FASEB journal : official publication of the Federation of American Societies for Experimental Biology. 32(9):4899-4916.
Abstract
Vitiligo is a depigmentary disorder that develops as a result of the progressive disappearance of epidermal melanocytes. Stress can precipitate or exacerbate a skin disease through psychosomatic mechanisms. Stress exposure induces vitiligo-like symptoms in mice, as cellular damage to melanocytes cause synthetic pigment loss. Stress also increases IL-17, IL-1β, and antimelanocyte IgG in model mice serum. Up-regulation of the IL-1β transcript in patients suggests its possible role in autoimmune pathogenesis of vitiligo. We demonstrate that IL-17 promoted IL-1β secretion from keratinocytes. Mitochondrial dysfunction, which can induce the excessive production of reactive oxygen species (ROS), is emerging as a mechanism that underlies various inflammatory and autoimmune diseases. In this study, we demonstrate that IL-17 inhibits melanogenesis of zebrafish, normal human epidermal melanocytes, and B16F10 cells. IL-17 increased mitochondrial dysfunction and ROS accumulation, which was related to autophagy induction. Autophagy is needed for autophagic apoptosis of B16F10 cells induced by IL-17. To inhibit ROS generation, B16F10 cells were pretreated with N-acetyl-l-cysteine (NAC), which inhibited autophagy process. 3-Methyladenine (3-MA) also had an inhibiting effect on autophagy. NAC or 3-MA pretreatments inhibited IL-17-mediated cell apoptosis. In summary, IL-17 induces the cellular stress microenvironment in melanocytes to promote autophagic cell apoptosis in vitiligo.-Zhou, J., An, X., Dong, J., Wang, Y., Zhong, H., Duan, L., Ling, J., Ping, F., Shang, J. IL-17 induces cellular stress microenvironment of melanocytes to promote autophagic cell apoptosis in vitiligo.
Genes / Markers
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Orthology
Engineered Foreign Genes
Mapping