THU0004\u2005MICRORNA-223 NEGATIVELY REGULATE GOUTY INFLAMMATION BY TARGETING THE NLRP3 INFLAMMASOME WITHOUT INFLUENCING IL-37 AND TGF-î’1

Abstract

Background MicroRNA-223 (miR-223) serves as an important regulator of inflammatory and immune responses and is implicated in several auto-inflammatory disorders[1]. To date, no relevant studies have reported the expression levels of miR-223 in gout patients or assessed whether miR-223 participates in negatively regulating gouty inflammation via regulating cytokines (such as IL-1β, tumor necrosis factor (TNF)-α, IL-37 and TGF-β1) by targeting the NLRP3 inflammasome. Objectives To determine the function of miR-223 in monosodium urate (MSU)-induced gouty inflammation. Methods: miR-223 was detected among 107 acute gout patients (AG), 58 intercritical gout patients (IG), and 75 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. Results 1. Expression of miR-223 in PBMCs among the AG, IG and HC groups(Figure1) Abstract THU0004 Figure 1 2. 2.Altered expression of miR-223, the NLRP3 inflammasome and cytokines in MSU-induced RAW264.7 murine macrophage inflammation(Figure2) Abstract THU0004 Figure 2 3. Effect of miR-223 on cytokine secretion from RAW264.7 macrophages treated with MSU(Figure3)Abstract THU0004 Figure 3 4. No effect on RAW264.7 macrophage apoptosis(Figure4)Abstract THU0004 Figure 4 5. Effect of miR-223 on NLRP3 inflammasome expression in RAW264.7 macrophages treated with MSU(Figure5)Abstract THU0004 Figure 5 Conclusion Our findings suggest that miR-223 provides negative feedback regulation of gouty inflammation development by suppressing production of IL-1β and TNF-α, but not by regulating IL-37 and TGF-β1, and that miR-223 regulates cytokine production by targeting the NLRP3 inflammasome. These findings provide novel insight into the regulatory role of miR-223 in the spontaneous resolution of acute gouty inflammation. Finally, these results suggest that targeting miR-223 in macrophages might be an effective therapeutic strategy for the treatment of gout flare. References [1] Henshall DC, Hamer HM, Pasterkamp RJ, Goldstein DB, Kjems J, Prehn JHM, Schorge S, Lamottke K, Rosenow F: MicroRNAs in epilepsy: pathophysiology and clinical utility. Lancet Neurol 2016; 15:1368-1376. Disclosure of Interests Yu-Feng Qing Grant/research support from: Sichuan Youth Science and Technology (2016JQ0053), and the Department of Science and Technology of Sichuan Province (2018JY0257), Dan Zhu: None declared, Ting Yi: None declared, Jian-Xiong Zheng: None declared, Qin Xiong: None declared, Quan-Bo Zhang: None declared