MicroRNA-486-5p suppresses inflammatory response by targeting FOXO1 in MSU-treated macrophages

Jianguo Hu1, Cheng Jin2, Li Fang3

  • 1Department of Rheumatology and Immunology, Xinyu People's Hospital, Xinyu, Jiangxi, China.

Autoimmunity
|October 13, 2022
PubMed

Insights

MicroRNA-486-5p (miR-486-5p) suppresses inflammation in gouty arthritis (GA) by targeting FOXO1. Upregulating miR-486-5p reduced inflammatory cytokines, offering a potential therapeutic target for GA.

Area of Science:

  • Immunology
  • Molecular Biology
  • Rheumatology

Background:

  • Gouty arthritis (GA) is characterized by monosodium urate (MSU) crystal deposition in joints.
  • MicroRNAs (miRNAs) play diverse roles in arthritis, but miR-486-5p function in GA remains unelucidated.
  • Understanding novel regulatory mechanisms is crucial for developing targeted GA therapies.

Purpose of the Study:

  • To investigate the role of microRNA-486-5p (miR-486-5p) in the inflammatory response of gouty arthritis.
  • To explore the potential molecular targets and pathways regulated by miR-486-5p in GA.
  • To assess the therapeutic potential of modulating miR-486-5p in GA models.

Main Methods:

  • Established *in vitro* GA cell models using THP-1 and J774A.1 cells treated with MSU crystals.
  • Quantified inflammatory cytokines (TNF-α, IL-8, IL-1β) using ELISA and RT-qPCR.
  • Assessed forkhead box protein O1 (FOXO1) levels via Western blot and its interaction with miR-486-5p using luciferase reporter assays.

Main Results:

  • MSU crystal treatment induced significant inflammatory responses in macrophage cell models.
  • miR-486-5p was downregulated by MSU treatment; its upregulation reduced inflammatory cytokine production.
  • FOXO1 was identified as a direct target of miR-486-5p, and its modulation reversed the anti-inflammatory effects.

Conclusions:

  • miR-486-5p acts as an inhibitor of the inflammatory response in gouty arthritis.
  • The anti-inflammatory effect of miR-486-5p is mediated through the negative regulation of FOXO1.
  • miR-486-5p represents a potential therapeutic target for managing gouty arthritis inflammation.

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