Zheng Shu-Cong, Zhu Xiao-Xia, Xue Yu, Zhang Li-Hong, Zou He-Jian, Qiu Jian-Hua, Liu Qiong
Division of Rheumatology, Huashan Hospital, Fudan University, Shanghai, China.
Institute of Rheumatology, Immunology and Allergy, Fudan University, Shanghai, China.
J Inflamm (Lond). 2015 Apr 10;12:30. doi: 10.1186/s12950-015-0070-7. eCollection 2015.
To investigate whether monosodium urate (MSU) crystals induce interleukin (IL)-1β in human fibroblast-like synoviocytes (FLS), and whether the NLRP3 inflammasome is involved in the inflammatory mechanism.
Human FLS isolated from explants of synovial tissue were stimulated with MSU crystals (0.001 to 0.5 mg/ml) for different time course (6 hours to 48 hours). The expressions of IL-1β, IL-6, TNF-α and NLRP3 were evaluated with ELISA, Western blot and quantitative real-time PCR.
Exposure of FLS to MSU crystals transiently induced a significant increase in IL-1β expression in culture medium with a peak at 6 h. The mRNA level of IL-1β in the FLS cells had a similar pattern at this time point. Changes in IL-6 and TNF-α expression were not observed. Simultaneously, intercellular pro-IL-1β was detected at 6 h. Furthermore, MSU crystals also induced NLRP3 mRNA and protein expression at 6 h to 48 h after MSU treatment.
MSU crystals directly increased IL-1β and intercellular NLRP3 expression in FLS cells. It is suggested that the NLRP3 inflammasome may be associated with IL-1β in FLS treated with MSU. Altogether, MSU could induce production and release of IL-1β through the NLRP3 inflammasome in human synoviocytes.
研究尿酸单钠（MSU）晶体是否能诱导人成纤维样滑膜细胞（FLS）产生白细胞介素（IL）-1β，以及NLRP3炎性小体是否参与炎症机制。
用MSU晶体（0.001至0.5mg/ml）刺激从滑膜组织外植体分离出的人FLS，刺激不同时间（6小时至48小时）。采用酶联免疫吸附测定（ELISA）、蛋白质免疫印迹法（Western blot）和定量实时聚合酶链反应（qRT-PCR）评估IL-1β、IL-6、肿瘤坏死因子-α（TNF-α）和NLRP3的表达。
FLS暴露于MSU晶体后，培养基中IL-1β表达短暂显著增加，6小时时达到峰值。此时FLS细胞中IL-1β的mRNA水平呈现相似模式。未观察到IL-6和TNF-α表达的变化。同时，在6小时时检测到细胞内的前体IL-1β。此外，MSU处理后6小时至48小时，MSU晶体还诱导了NLRP3 mRNA和蛋白表达。
MSU晶体直接增加了FLS细胞中IL-1β和细胞内NLRP3的表达。提示NLRP3炎性小体可能与MSU处理的FLS中的IL-1β有关。总之，MSU可通过NLRP3炎性小体诱导人滑膜细胞产生并释放IL-1β。
