Department of Rheumatology and Immunology, Affiliated Hospital of North Sichuan Medical College, Sichuan Province, Nanchong, 637000, China.
Henry Ford Immunology Program, Henry Ford Health System, 1 Ford Place, Detroit, MI, 48202, USA.
Arthritis Res Ther. 2018 Jul 11;20(1):144. doi: 10.1186/s13075-018-1550-y.
The findings of a previous study by Jin et al. have shown that microRNA (miR)-155 was upregulated in patients with acute gouty arthritis and enhanced the proinflammatory cytokines. There is no direct evidence to support that miR-155 is indeed involved in monosodium urate (MSU)-induced inflammatory responses in vivo. The aim of this study was to investigate the role of miR-155 knock-out (KO) or knock-in (KI) mice in MSU-induced animal models to mimic acute gout.
MiR-155 expression in cultured bone marrow-derived macrophages (BMDMs) from miR-155 KO, miR-155 KI, and wild-type (WT) mice treated with MSU crystals in vitro was detected by real-time quantitative polymerase chain reaction (qPCR). MiR-155 KO and WT mice were used to induce an acute gouty inflammatory response with MSU crystals including models of foot pad inflammation, ankle arthritis, air pouch inflammation, and peritonitis. Furthermore, the proinflammatory interleukin (IL)-1β levels in lavage fluids from air pouch and peritoneal cavity models were measured by enzyme-linked immunosorbent assay (ELISA), and tumor necrosis factor (TNF)-α production from BMDMs of miR-155 KI mice treated with MSU were measured by flow cytometry.
MiR-155 expression was quickly upregulated in BMDMs from WT mice following MSU treatment in vitro. In comparison with WT mice in vivo, the swelling index of miR-155 KO mice showed no significant difference in the murine foot pad and ankle arthritis models for the indicated different time points. There were similar changes in total cell numbers of lavage fluids in the air pouch and peritoneal cavity models between miR-155 KO and WT mice following MSU crystal injection. Moreover, the IL-1β levels of lavage fluids in the air pouch and peritonitis models from miR-155 KO mice were almost the same as those from WT mice. TNF-α levels were comparable from BMDMs treated with MSU crystals in vitro between miR-155 KI mice and WT mice.
MiR-155 is dispensable in MSU-induced gouty inflammation in mice. Deletion of miR-155 might not be an effective therapeutic approach to relieve the inflammation in acute gout.
Jin 等人之前的研究结果表明，微小 RNA（miR）-155 在急性痛风性关节炎患者中上调，并增强了前炎性细胞因子。没有直接证据表明 miR-155 确实参与了体内尿酸单钠（MSU）诱导的炎症反应。本研究旨在探讨 miR-155 敲除（KO）或敲入（KI）小鼠在 MSU 诱导的动物模型中模拟急性痛风的作用。
通过实时定量聚合酶链反应（qPCR）检测体外用 MSU 晶体处理的 miR-155 KO、miR-155 KI 和野生型（WT）小鼠骨髓来源巨噬细胞（BMDM）中 miR-155 的表达。用 MSU 晶体诱导 miR-155 KO 和 WT 小鼠发生急性痛风性炎症反应，包括足垫炎症、踝关节关节炎、气囊炎症和腹膜炎模型。此外，通过酶联免疫吸附试验（ELISA）测量气囊和腹腔模型灌洗液中促炎白细胞介素（IL）-1β水平，通过流式细胞术测量 MSU 处理的 miR-155 KI 小鼠 BMDM 中肿瘤坏死因子（TNF）-α的产生。
MSU 体外处理后，WT 小鼠的 BMDM 中 miR-155 表达迅速上调。与体内 WT 小鼠相比，在不同时间点的小鼠足垫和踝关节关节炎模型中，miR-155 KO 小鼠的肿胀指数无显著差异。在 MSU 晶体注射后，气囊和腹腔模型中 miR-155 KO 和 WT 小鼠的灌洗液总细胞数也有类似的变化。此外，miR-155 KO 小鼠气囊和腹膜炎模型灌洗液中的 IL-1β 水平与 WT 小鼠几乎相同。从体外用 MSU 晶体处理的 BMDM 中，miR-155 KI 小鼠和 WT 小鼠的 TNF-α 水平相当。
在 MSU 诱导的小鼠痛风性炎症中，miR-155 是可有可无的。缺失 miR-155 可能不是缓解急性痛风炎症的有效治疗方法。
