Increased FURIN expression in rheumatoid arthritis patients and its anti-inflammatory effect

J Clin Lab Anal. 2020 Dec;34(12):e23530. doi: 10.1002/jcla.23530. Epub 2020 Aug 25.

Abstract

Background: FURIN belongs to the proprotein convertase family that processes proproteins and is involved in many diseases. However, the role of FURIN in rheumatoid arthritis (RA) remains unknown. In this study, we investigated the association between circulating FURIN and disease activity in patients with RA and the effect of FURIN in THP-1-derived macrophages.

Methods: A total of 108 RA patients and 39 healthy controls participants were included in this study. RA patients were divided into four disease activity groups determined by the Disease Activity Score of 28 joints (DAS28). FURIN expression in peripheral blood mononuclear cells (PBMCs) and serum was detected by using quantitative real-time polymerase chain reaction (qRT-PCR) and enzyme-linked immunosorbent assay (ELISA), respectively. Western blotting and qRT-PCR were used to detect cytokines level after interfering FURIN expressed in THP-1-derived macrophages.

Results: Both FURIN mRNA and protein levels were significantly higher in RA patients than in healthy controls participants (P < .001). No significant difference in FURIN expression was observed among the four RA groups (P > .05). Spearman correlation revealed that FURIN positively correlated with transforming growth factor-β1(TGF-β1), rheumatoid factor (RF), and anti-cyclic citrullinated peptide (anti-CCP). Moreover, the inhibition of FURIN in THP-1-derived macrophages promoted the caspase-1 and IL-1β expression (P < .05).

Conclusion: FURIN levels were significantly increased in the peripheral blood of RA patients and were not associated with disease activity. The inhibition of FURIN in THP-1-derived macrophages with elevated IL-1β levels shows that FURIN may have an anti-inflammatory effect.

Keywords: DAS28; FURIN; THP-1 derived macrophages; rheumatoid arthritis.

MeSH terms

  • Adult
  • Aged
  • Anti-Inflammatory Agents / analysis
  • Anti-Inflammatory Agents / metabolism
  • Arthritis, Rheumatoid* / epidemiology
  • Arthritis, Rheumatoid* / genetics
  • Arthritis, Rheumatoid* / metabolism
  • Female
  • Furin* / analysis
  • Furin* / genetics
  • Furin* / metabolism
  • Humans
  • Macrophages / chemistry
  • Macrophages / metabolism
  • Male
  • Middle Aged
  • RNA, Messenger / analysis
  • RNA, Messenger / genetics
  • RNA, Messenger / metabolism
  • THP-1 Cells

Substances

  • Anti-Inflammatory Agents
  • RNA, Messenger
  • FURIN protein, human
  • Furin