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

Min-Chan Park1, Oh Chan Kwon2, Sang-Won Lee2

  • 1Division of Rheumatology, Department of Internal Medicine, Yonsei University College of Medicine, Seoul, South Korea. mcpark@yuhs.ac.

Abstract

Insights

MicroRNA-451 (miR-451) levels were lower and macrophage migration inhibitory factor (MIF) levels higher in ankylosing spondylitis (AS) patients. Increasing miR-451 suppressed MIF and inflammation, suggesting a therapeutic target for AS.

Area of Science:

  • Immunology
  • Genetics
  • Rheumatology

Background:

  • Ankylosing spondylitis (AS) is a chronic inflammatory disease.
  • Biomarkers for AS disease activity and progression are needed.
  • The roles of microRNA-451 (miR-451) and macrophage migration inhibitory factor (MIF) in AS are not fully understood.

Purpose of the Study:

  • To investigate the associations of miR-451 and MIF with disease activity, radiographic progression, and cytokine levels in AS.
  • To explore the potential of miR-451 as a therapeutic target in AS.

Main Methods:

  • Peripheral blood mononuclear cells (PBMCs) were isolated from AS patients, peripheral spondyloarthritis (pSpA) patients, and healthy controls.
  • Expression levels of miR-451 and MIF were quantified using qRT-PCR.
  • Cytokine concentrations (TNF-α, IL-6) and MIF levels in supernatants were measured by ELISA.
  • AS PBMCs were transfected with miR-451 mimic to assess its effect on MIF and cytokine levels.

Main Results:

  • miR-451 expression was lower, while MIF expression was significantly higher in AS PBMCs compared to controls.
  • MIF, TNF-α, and IL-6 levels were elevated in AS PBMCs.
  • Elevated MIF correlated with higher radiographic damage (mSASSS ≥ 12).
  • miR-451 mimic transfection reduced MIF, TNF-α, and IL-6 mRNA and protein levels.

Conclusions:

  • MIF is elevated in AS patients with significant radiographic damage.
  • Overexpression of miR-451 suppresses MIF and inflammatory cytokine production in AS.
  • The miR-451/MIF axis represents a potential novel therapeutic target for AS treatment.

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