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