AUTHOR=Zhang Quan-Bo , Zhu Dan , Dai Fei , Huang Yu-Qin , Zheng Jian-Xiong , Tang Yi-Ping , Dong Zeng-Rong , Liao Xia , Qing Yu-Feng 

TITLE=MicroRNA-223 Suppresses IL-1β and TNF-α Production in Gouty Inflammation by Targeting the NLRP3 Inflammasome

JOURNAL=Frontiers in Pharmacology

VOLUME=12

YEAR=2021

URL=https://www.frontiersin.org/journals/pharmacology/articles/10.3389/fphar.2021.637415

DOI=10.3389/fphar.2021.637415

ISSN=1663-9812

ABSTRACT=<p><bold>Introduction:</bold> MicroRNA-223 (MiR-223) serves as an important regulator of inflammatory and immune responses and is implicated in several auto-inflammatory disorders. Here, we measured miR-223 expression in acute and intercritical gout patients, after which we used RAW264.7 macrophages transfected with a miR-223 mimic/inhibitor to determine the function of miR-223 in monosodium urate (MSU)-induced gouty inflammation.</p><p><bold>Methods and Results:</bold> MiR-223 was detected among 122 acute gout patients (AG), 118 intercritical gout patients (IG), and 125 healthy subjects (HC). RAW264.7 macrophages were cultured and treated with MSU. Over-expression or under-expression of miR-223 was inducted in RAW264.7 macrophages to investigate the function of miR-223. Real-time quantitative PCR, ELISA and western blotting were used to determine the expression levels of miR-223, cytokines and the NLRP3 inflammasome (NLRP3, ASC, and caspase-1). MiR-223 expression was significantly decreased in the AG group in comparison with the IG and HC groups (<italic>p</italic> &lt; 0.001, respectively). Up-regulated expression of miR-223 was observed after acute gout remission in comparison with that observed during gout flares in 30 paired cases (<italic>p</italic> &lt; 0.001). The abundance of the NLRP3 inflammasome and cytokines was significantly increased after RAW264.7 macrophages were treated with MSU (<italic>p</italic> &lt; 0.01, respectively), while that of miR-223 was significantly reduced (<italic>p</italic> &lt; 0.01). Up-regulation of miR-223 decreased the concentrations of IL-1β and TNF-α, as well as the NLRP3 inflammasome expression (p &lt; 0.01, respectively), while IL-37 and TGF-β1 levels were unchanged (<italic>p</italic> &gt; 0.05, respectively). Under-expression of miR-223 increased the concentrations of IL-1β and TNF-α, as well as NLRP3 inflammasome expression (<italic>p</italic> &lt; 0.01, respectively), while IL-37 and TGF-β1 levels were not influenced (<italic>p</italic> &gt; 0.05, respectively).</p><p><bold>Conclusion:</bold> These findings suggest that miR-223 provides negative feedback regulation of the development of gouty inflammation by suppressing production of IL-1β and TNF-α, but not by regulating IL-37 and TGF-β1. Moreover, miR-223 regulates cytokine production by targeting the NLRP3 inflammasome.</p>