Ma Zhen-Zhen, Sun Hong-Sheng, Lv Ji-Cai, Guo Lei, Yang Qing-Rui
Department of Rheumatology and Immunology, Shandong Provincial Hospital Affiliated to Shandong University, Jinan, 250021 Shandong China.
J Inflamm (Lond). 2018 Sep 3;15:16. doi: 10.1186/s12950-018-0192-9. eCollection 2018.
The aim of the study was to investigate the expression of the NEK7-NLRP3 inflammasome signaling pathway in the peripheral blood mononuclear cells (PBMCs) of patients with systemic lupus erythematosus (SLE), as well as its clinical significance.
A total of 38 SLE patients and 33 healthy volunteers were recruited. Real time PCR and western blotting were performed to determine mRNA and protein levels of , NLRP3 inflammasome components (, , and ), and downstream cytokines ( and ) in PBMCs from the two groups. ELISA was used to detect serum levels of and . The same methods were used to detect changes in the above indices in the 25 SLE patients after treatment. Correlations between clinical and laboratory parameters were also analyzed.
Compared to those in healthy controls, levels of and were lower in SLE patients; however, , , and were expressed at higher levels. mRNA levels of , , and were inversely correlated with disease activity, whereas a positive correlation was observed with and . After treatment, mRNA levels of and increased, whereas , , and decreased significantly. Compared to those in SLE patients without renal damage, patients with lupus nephritis (LN) exhibited lower mRNA levels of , , and but higher levels of , , and .
Results indicate that the expression of the NEK7-NLRP3 complex might play a protective role in the pathogenesis of SLE and is inversely correlated with disease activity. A positive effect of on was observed, and the low expression of in SLE patients might be related to the low expression of . Overexpression of in SLE patients mediates the maturation and release of and , and contributes to the pathogenesis of SLE and LN.
本研究旨在探讨系统性红斑狼疮(SLE)患者外周血单个核细胞(PBMCs)中NEK7-NLRP3炎症小体信号通路的表达及其临床意义。
共招募38例SLE患者和33名健康志愿者。采用实时荧光定量PCR和蛋白质印迹法检测两组PBMCs中NEK7、NLRP3炎症小体成分(NLRP3、ASC和pro-caspase-1)及下游细胞因子(IL-1β和IL-18)的mRNA和蛋白质水平。采用酶联免疫吸附测定(ELISA)法检测血清中IL-1β和IL-18水平。采用相同方法检测25例SLE患者治疗后上述指标的变化。同时分析临床和实验室参数之间的相关性。
与健康对照相比,SLE患者中NEK7和IL-18水平较低;然而,NLRP3、ASC和pro-caspase-1表达水平较高。NEK7、NLRP3和ASC的mRNA水平与疾病活动度呈负相关,而与IL-1β和IL-18呈正相关。治疗后,NEK7和IL-18的mRNA水平升高,而NLRP3、ASC和pro-caspase-1显著降低。与无肾脏损害的SLE患者相比,狼疮性肾炎(LN)患者的NEK7、NLRP3和ASC的mRNA水平较低,但IL-1β、IL-18和pro-caspase-1水平较高。
结果表明,NEK7-NLRP3复合物的表达可能在SLE发病机制中起保护作用,且与疾病活动度呈负相关。观察到NEK7对IL-18有正向作用,SLE患者中IL-18的低表达可能与NEK7的低表达有关。SLE患者中NEK7的过表达介导了IL-1β和IL-18的成熟和释放,促进了SLE和LN的发病机制。