Document Detail


IL-17-induced MiR-873 attributes to the pathogenesis of experimental autoimmune encephalomyelitis by targeting A20 ubiquitin editing enzyme.
MedLine Citation:
PMID:  25183005     Owner:  NLM     Status:  Publisher    
Abstract/OtherAbstract:
Interleukin 17 (IL-17), produced mainly by T helper (Th) 17 cells, is increasingly recognized as a key regulator in various autoimmune diseases, including human multiple sclerosis (MS), and its animal model, experimental autoimmune encephalomyelitis (EAE). Although several microRNAs (miRNAs) with aberrant expression have been shown to contribute to the pathogenesis of MS and EAE, the mechanisms underlying the regulation of abnormal miRNA expression in astrocytes upon IL-17 stimulation remain unclear. In the present study, we detected the changes of miRNA expression profiles both in the brain tissue of EAE mice and in cultured mouse primary astrocytes stimulated with IL-17, and identified miR-873 as one of co-up-regulated miRNA in vivo and in vitro. The overexpression of miR-873, demonstrated by targeting A20 (TNFα-induced protein 3, TNFAIP3), remarkably reduced the A20 level and promoted NF-қB activation in vivo and in vitro, as well as increased the production of inflammatory cytokines and chemokines (i.e. IL-6, TNF-α, MIP-2 and MCP-1/5). More importantly, silencing the endogenous miR-873 or A20 gene with lentiviral vector of miR-873 sponge (LV-miR-873 sponge) or short hairpin RNA (shRNA) of A20 (LV-A20 shRNA) in vivo significantly lessened or aggravated inflammation and demyelination in the central nervous system (CNS) of EAE mice, respectively. Taken together, these findings indicate that miR-873 induced by IL-17 stimulation promotes the production of inflammatory cytokines and aggravates pathological process of EAE mice through A20/NF-қB pathway, which providing a new insight into the mechanism of inflammatory damage in MS.
Authors:
Xiaomei Liu; Fengxia He; Rongrong Pang; Dan Zhao; Wen Qiu; Kai Shan; Jing Zhang; Yanlai Lu; Yan Li; Yingwei Wang
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Publication Detail:
Type:  JOURNAL ARTICLE     Date:  2014-9-2
Journal Detail:
Title:  The Journal of biological chemistry     Volume:  -     ISSN:  1083-351X     ISO Abbreviation:  J. Biol. Chem.     Publication Date:  2014 Sep 
Date Detail:
Created Date:  2014-9-3     Completed Date:  -     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  2985121R     Medline TA:  J Biol Chem     Country:  -    
Other Details:
Languages:  ENG     Pagination:  -     Citation Subset:  -    
Copyright Information:
Copyright © 2014, The American Society for Biochemistry and Molecular Biology.
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