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MiR-451 Suppresses Inflammatory Responses in Ankylosing Spondylitis by Targeting Macrophage Migration Inhibitory Factor

Authors
 Min-Chan Park  ;  Oh Chan Kwon  ;  Sang-Won Lee  ;  Jason Jungsik Song  ;  Yong-Beom Park 
Citation
 CLINICAL AND EXPERIMENTAL RHEUMATOLOGY, Vol.38(2) : 275-281, 2020-03 
Journal Title
 CLINICAL AND EXPERIMENTAL RHEUMATOLOGY 
ISSN
 0392-856X 
Issue Date
2020-03
MeSH
Humans ; Leukocytes, Mononuclear* ; Macrophage Migration-Inhibitory Factors / genetics ; Macrophage Migration-Inhibitory Factors / metabolism* ; MicroRNAs* / genetics ; MicroRNAs* / metabolism ; Spondylitis, Ankylosing* / genetics ; Spondylitis, Ankylosing* / immunology ; Spondylitis, Ankylosing* / metabolism ; Tumor Necrosis Factor-alpha
Abstract
Objectives: To investigate the associations of miR-451 and macrophage migration inhibitory factor (MIF) with disease activity, radiographic progression, and cytokine levels of ankylosing spondylitis (AS). Methods: Peripheral blood mononuclear cells (PBMCs) were isolated and cultured from 43 AS patients, 11 peripheral spondyloarthritis (pSpA) patients, and 31 healthy controls. ASDAS-CRP and mSASSS were assessed at the time of blood sampling. Expression levels of miR-451 and MIF were determined using quantitative real-time PCR, and the supernatant concentrations of MIF and cytokines were measured using ELISA. After transfection of miR-451 synthetic mimic or FAM-labelled negative control mimic to AS PBMCs, MIF and cytokine levels were determined using quantitative real-time PCR or ELISA. Results: Level of miR-451 expression was lower in AS PBMCs than in pSpA and control PBMCs, while MIF expression was significantly increased in AS PBMCs compared with those in pSpA and control PBMCs. MIF, TNF-α, and IL-6 concentrations in cell supernatants of AS PBMCs were significantly higher than those of pSpA and control PBMCs. miR-451 expression level did not show significant correlation with clinical parameters, but MIF expression level was elevated in PBMCs from AS patients with high mSASSS (12 or more). Treatment of AS PBMCs with the miR-451 synthetic miRNA mimic significantly reduced mRNA expression levels and cell supernatant concentrations of MIF, TNF-α, and IL-6. Conclusions: The MIF level was elevated in AS patients with greater radiographic damage and overexpression of miR-451 suppressed the MIF and inflammatory cytokine levels. These findings suggest miR-451/MIF may be a novel therapeutic target in the treatment of AS.
Full Text
https://www.clinexprheumatol.org/abstract.asp?a=13970
Appears in Collections:
1. College of Medicine (의과대학) > Dept. of Internal Medicine (내과학교실) > 1. Journal Papers
Yonsei Authors
Kwon, Oh Chan(권오찬)
Park, Min Chan(박민찬) ORCID logo https://orcid.org/0000-0003-1189-7637
Park, Yong Beom(박용범)
Song, Jason Jungsik(송정식) ORCID logo https://orcid.org/0000-0003-0662-7704
Lee, Sang-Won(이상원) ORCID logo https://orcid.org/0000-0002-8038-3341
URI
https://ir.ymlib.yonsei.ac.kr/handle/22282913/175984
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