Role of miR-146a in regulation of the acute inflammatory response to monosodium urate crystals. Issue 4 (2nd February 2015)

• Record Type: Journal Article
• Authors: Dalbeth, Nicola; Pool, Bregina; Shaw, Odette M; Harper, Jacquie L; Tan, Paul; Franklin, Christopher; House, Meaghan E; Cornish, Jillian; Naot, Dorit
• Is Part Of: Annals of the rheumatic diseases. Volume 74:Issue 4(2015)
• Page Start: 786
• Page End: 790
• Publication Date: 2015-02-02
• Subjects: Gout -- Inflammation -- Cytokines; Rheumatism -- Periodicals; 616.723005
• DOI: 10.1136/annrheumdis-2014-205409
• Languages: English
• ISSNs: 0003-4967

Abstract

Abstract : Objectives: MicroRNAs (miRNA) are small non-coding RNAs that function as post-transcriptional repressors of gene expression. We hypothesised that miRNA regulate gene expression of proinflammatory cytokines in response to monosodium urate (MSU) crystals. Methods: We stimulated human monocytic THP-1 cells with MSU crystals and examined miRNA and proinflammatory cytokine gene expression. The effects of miR-146a overexpression were examined by transfecting THP-1 cells with miR-146a precursor. miR-146a expression was examined in the urate peritonitis model, in peripheral blood mononuclear cells from people with gout and control participants, and in gouty tophus samples. Results: MSU crystals increased miR-146a expression in THP-1 cells, but not other miRNA implicated in interleukin (IL)-1β regulation. Overexpression of miR-146a expression reduced MSU crystal-induced IL-1β, tumour necrosis factor-α (TNFα), monocyte chemoattractant protein-1 (MCP-1) and IL-8 gene expression. In the urate peritonitis model, reduced miR-146a expression was observed during the acute inflammatory response to MSU crystal injection. In people with intercritical gout, peripheral blood mononuclear cells expressed significantly higher levels of miR-146a, compared with normouricaemic and hyperuricaemic control participants and those with acute gout flares. Expression of miR-146a was also observed in all tophus samples. Conclusions: Collectively, these data suggest that miR-146a is a transcriptional brake that is lost during the acute inflammatory response to MSU crystals.