BACKGROUND 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. METHODS 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 NEK7, NLRP3 inflammasome components (NLRP3, ASC, and Caspase-1), and downstream cytokines (IL-1b and IL-18) in PBMCs from the two groups. ELISA was used to detect serum levels of IL-1b and IL-18. 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. RESULTS Compared to those in healthy controls, levels of NEK7, NLPR3, and ASC were lower in SLE patients; however, Caspase-1, IL-1b, and IL-18 were expressed at higher levels. mRNA levels of NEK7, NLRP3, and ASC were inversely correlated with disease activity, whereas a positive correlation was observed with IL-1b and IL-18. After treatment, mRNA levels of NEK7 and NLRP3 increased, whereas Caspase-1, IL-1b, and IL-18 decreased significantly. Compared to those in SLE patients without renal damage, patients with lupus nephritis (LN) exhibited lower mRNA levels of NEK7, NLRP3, and ASC but higher levels of Caspase-1, IL-1b, and IL-18. CONCLUSIONS 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 NEK7 on NLRP3 was observed, and the low expression of NLRP3 in SLE patients might be related to the low expression of NEK7. Overexpression of Caspase-1 in SLE patients mediates the maturation and release of IL-1b and IL-18, and contributes to the pathogenesis of SLE and LN.

中文翻译：

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NEK7-NLRP3炎症小体信号通路在系统性红斑狼疮患者中的表达及临床意义

背景 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。方法共招募38名SLE患者和33名健康志愿者。进行实时 PCR 和蛋白质印迹以确定两组 PBMC 中 NEK7、NLRP3 炎性体成分（NLRP3、ASC 和 Caspase-1）和下游细胞因子（IL-1b 和 IL-18）的 mRNA 和蛋白质水平。ELISA用于检测IL-1b和IL-18的血清水平。用同样的方法检测25例SLE患者治疗后上述指标的变化。还分析了临床和实验室参数之间的相关性。结果 与健康对照组相比，SLE 患者的 NEK7、NLPR3 和 ASC 水平较低；然而，Caspase-1、IL-1b 和 IL-18 的表达水平较高。NEK7、NLRP3 和 ASC 的 mRNA 水平与疾病活动呈负相关，而与 IL-1b 和 IL-18 呈正相关。治疗后，NEK7 和 NLRP3 的 mRNA 水平升高，而 Caspase-1、IL-1b 和 IL-18 显着降低。与没有肾损伤的 SLE 患者相比，狼疮性肾炎 (LN) 患者的 NEK7、NLRP3 和 ASC mRNA 水平较低，但 Caspase-1、IL-1b 和 IL-18 水平较高。结论 结果表明，NEK7-NLRP3复合物的表达可能在SLE的发病机制中起保护作用，并且与疾病活动度呈负相关。观察到 NEK7 对 NLRP3 的积极影响，SLE患者NLRP3的低表达可能与NEK7的低表达有关。SLE 患者中 Caspase-1 的过表达介导 IL-1b 和 IL-18 的成熟和释放，并有助于 SLE 和 LN 的发病机制。