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SAT0528 Role of Micrornas in Regulation of the Acute Inflammatory Response to Monosodium Urate Crystals
  1. N. Dalbeth,
  2. B. Pool,
  3. C. Franklin,
  4. M.E. House,
  5. J. Cornish,
  6. D. Naot
  1. University of Auckland, Auckland, New Zealand

Abstract

Background MicroRNAs (miRNA) are a class of small, evolutionary conserved non-coding RNAs that function as posttranscriptional repressors of gene expression.

Objectives To test the hypothesis that miRNA play a role in regulating gene expression of pro-inflammatory cytokines in response to MSU crystals.

Methods We stimulated human monocytic THP-1 cells with monosodium urate (MSU) crystals and/or interleukin (IL)-1β, and examined miRNA and pro-inflammatory cytokine gene expression using quantitative real-time PCR. The effects of miR-146a over-expression were examined by transfecting THP-1 cells with miR-146a precursor. The relative expression of miR-146a was also examined in tophus samples and in peripheral blood mononuclear cells (PBMC) from people with intercritical gout, and normouricaemic and hyperuricaemic control participants.

Results In THP-1 cells, MSU crystals increased miR-146a expression, but not other miRNA implicated in IL-1 regulation. miR-146a and IL-1β expression were both maximal 20 hours after MSU crystal stimulation. Culture with IL-1β alone led to an increase in miR-146a, but addition of IL-1β did not further increase miR-146a expression following culture with MSU crystals. Inhibition of IL-1β using IL-1ra did not inhibit MSU crystal induced miR-146a expression. Transfection of THP-1 cells with miR-146a precursor led to high levels of miR-146a expression and reduced MSU crystal-induced IL-1β, TNFα, MCP-1 and IL-8 gene expression. In people with intercritical gout, PBMC expressed higher levels of miR-146a, compared with both healthy normouricaemic and hyperuricaemic control participants (ANOVA p<0.0001). Similar concentrations of IL-1β gene expression were observed in the three groups. Expression of miR-146a was also observed in tophus samples.

Conclusions Together, these data suggest that miR-146a acts as a transcriptional brake in the acute inflammatory response to MSU crystals.

Disclosure of Interest None declared

DOI 10.1136/annrheumdis-2014-eular.3400

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