MicroRNA-302b negatively regulates IL-1β production in response to MSU crystals by targeting IRAK4 and EphA2

Abstract Background Interleukin-1β (IL-1β) is a pivotal proinflammatory cytokine that is strongly associated with the inflammation of gout. However, the underlying mechanism through which the production of IL-1β is regulated has not been fully elucidated. Our previous work identified that miR-302b had an important immune regulatory role in bacterial lung infections. This study was conducted to evaluate the function of miR-302b on monosodium urate (MSU) crystal-induced inflammation and its mechanism. Methods The expression pattern and the immune-regulatory role of miR-302b were evaluated both in vitro and in vivo. The functional targets of miR-302b were predicted by bioinformatics, and then validated by genetic approaches. In addition, the clinical feature of miR-302b was analyzed using serum samples of patients with gouty arthritis. Results The extremely high expression of miR-302b was observed in both macrophages and mouse air membranes treated with MSU. Intriguingly, overexpression of miR-302b regulated NF-κB and caspase-1 signaling, leading to significantly attenuate MSU-induced IL-1β. By genetic analysis, miR-302b exhibited inhibitory function on IRAK4 and EphA2 by binding to their 3′-UTR regions. Corporately silencing IRAK4 and EphA2 largely impaired MSU-induced IL-1β protein production. Moreover, it was also found that miR-302b and EphA2 suppressed the migration of macrophages. Finally, it was observed that high expression of miR-302b was a general feature in patients with gouty arthritis. Conclusions These results suggest that miR-302b can regulate IL-1β production in MSU-induced inflammation by targeting NF-κB and caspase-1 signaling, and may be a potential therapeutic target for gouty arthritis

Additional file 1: Table S1. of MicroRNA-302b negatively regulates IL-1β production in response to MSU crystals by targeting IRAK4 and EphA2

presenting patient characteristics, Table S2. presenting primers used in this study, Figure S1. showing function of IRAK4 and EphA2 on level of cleaved caspase-1 p20 and p-NF-κB in THP-1 cells, respectively, Figure S2. showing miR-302b represses MSU-induced IL-1β expression, and Figure S3. showing miR-302b serum levels in gouty arthritis patients and healthy controls. (DOCX 1301 kb