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

ABSTRACT: Interleukin-1? (IL-1?) is a pivotal proinflammatory cytokine that is strongly associated with the inflammation of gout. However, the underlying mechanism through which the production of IL-1? 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.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.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-?B and caspase-1 signaling, leading to significantly attenuate MSU-induced IL-1?. 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-1? 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.These results suggest that miR-302b can regulate IL-1? production in MSU-induced inflammation by targeting NF-?B and caspase-1 signaling, and may be a potential therapeutic target for gouty arthritis.

SUBMITTER: Ma T 

PROVIDER: S-EPMC5828083 | biostudies-other | 2018 Feb

REPOSITORIES: biostudies-other