IL-33 enhances macrophage release of IL-1β and promotes pain and inflammation in gouty arthritis
IL-33 enhances macrophage release of IL-1β and promotes pain and inflammation in gouty arthritis
复制标题
白细胞介素 - 33（IL - 33）可增强巨噬细胞白细胞介素 - 1β（IL - 1β）的释放，并加剧痛风性关节炎的疼痛与炎症。
DOI：
10.1007/s00011-020-01399-x
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发表时间：
2020-09-04
影响因子：
6.7
通讯作者：
Verri Jr, Waldiceu A.
中科院分区：
文献类型：
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作者：
Fattori, Victor;Staurengo-Ferrari, Larissa;Verri Jr, Waldiceu A.
目的探讨IL-33在痛风性关节炎中的作用。实验用Balb/c（野生型）小鼠174只，ST2（-/-）小鼠54只。体外实验采用骨髓源性巨噬细胞（bmmdms）进行。采用痛风性关节炎（n = 7）和骨关节炎（n = 8）住院患者的滑液样本测量IL-33和sST2水平。方法在小鼠膝关节内注射尿酸钠（MSU）晶体诱导痛风。采用电子von Frey法和静态负重法测定疼痛。中性粒细胞募集通过H&E染色、Rosenfeld染色玻片和MPO活性测定。ELISA法检测细胞因子和sST2。测定IL-33在BMDM中的启动效应。结果痛风患者滑液中IL-33水平和中性粒细胞计数高于骨关节炎患者。在小鼠中，ST2的缺失可以防止机械性疼痛、膝关节水肿、中性粒细胞向膝关节募集，并降低IL-1 β和超氧阴离子水平。在巨噬细胞中，IL-33增强了IL-1 β和tnf - α的释放，ST2（-/-）的BMDMs在MSU晶体刺激后显示这些细胞因子水平降低。结论IL-33在MSU晶体刺激下促进巨噬细胞产生细胞因子，介导痛风疼痛和炎症。
Objective To investigate the role of IL-33 in gouty arthritis. Material 174 Balb/c (wild-type) and 54 ST2(-/-)mice were used in this study. In vitro experiments were conducted in bone marrow-derived macrophages (BMDMs). Synovial fluid samples from gouty arthritis (n = 7) and osteoarthritis (n = 8) hospital patients were used to measure IL-33 and sST2 levels. Methods Gout was induced by injection of monosodium urate (MSU) crystals in the knee joint of mice. Pain was determined using the electronic von Frey and static weight bearing. Neutrophil recruitment was determined by H&E staining, Rosenfeld staining slides, and MPO activity. ELISA was used for cytokine and sST2 measurement. The priming effect of IL-33 was determined in BMDM. Results Synovial fluid of gout patients showed higher IL-33 levels and neutrophil counts than osteoarthritis patients. In mice, the absence of ST2 prevented mechanical pain, knee joint edema, neutrophil recruitment to the knee joint, and lowered IL-1 beta and superoxide anion levels. In macrophages, IL-33 enhanced the release of IL-1 beta and TNF-alpha, and BMDMs from ST2(-/-)showed reduced levels of these cytokines after stimulus with MSU crystals. Conclusion IL-33 mediates gout pain and inflammation by boosting macrophages production of cytokines upon MSU crystals stimulus.