MiR-451 suppresses inflammatory responses in ankylosing spondylitis by targeting macrophage migration inhibitory factor

Abstract

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). 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. 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. 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.