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miR-146a 与系统性红斑狼疮患者促炎细胞因子之间的串扰。

Crosstalk between miR-146a and pro-inflammatory cytokines in patients with systemic lupus erythematosus.

机构信息

Molecular Biology Department, Genetic Engineering and Biotechnology Research Institute, 392053Sadat City University, Egypt.

Rheumatology and Rehabilitation Department, Faculty of Medicine, 63527Cairo University, Cairo, Egypt.

出版信息

Int J Immunopathol Pharmacol. 2023 Jan-Dec;37:3946320231154998. doi: 10.1177/03946320231154998.

Abstract

microRNA-146a (miR-146a) plays an essential role in immune anomalies and organ injury of systemic lupus erythematosus (SLE) by regulating the disease's inflammation and complications. Here, we analyzed the expression of miR-146a in SLE and a panel of pro-inflammatory cytokines (IL-1, IL-6, IL-8, IL-17, and TNF-α). Association between all measured parameters and the disease's clinical manifestation and response to treatment was monitored. Our study populations were 113 SLE patients and 104 healthy volunteers. miR-146a expression in peripheral blood mononuclear cells (PBMCs) was measured by quantitative real-time PCR (RT-qPCR). The content of the plasma cytokines (IL-1β, IL-6, IL-8, IL-17, and TNF-α) was detected by enzyme-linked immunosorbent assay (ELISA). Compared with healthy controls, miR-146a expression was significantly increased ( < 0.05) in lupus patients. The analysis of the receiver operator characteristic curve (ROC) of miR-146a showed 91% sensitivity and 70% specificity. IL-1β, IL-6, and IL-17 cytokines were significantly increased ( < 0.001), while IL-8 and TNF-α were significantly decreased ( < 0.001) in SLE patients against controls. The expression of miR-146a and TNF-α was upregulated considerably in SLE patients with severe disease activity. miR-146a expression was positively correlated with IL-6. Our results pointed to the elevation of miR-146a as a trade marker of SLE patients. Reduction of IL-8 and TNF-α in combination with an elevation of IL-1β, IL-6, and IL-17 might refer to miR-146a's dual effect in controlling inflammation in lupus. Although we shed some light on the role of miR-146a in SLE, further study is recommended to improve our results.

摘要

miR-146a(miR-146a)通过调节疾病的炎症和并发症,在系统性红斑狼疮(SLE)的免疫异常和器官损伤中发挥重要作用。在这里,我们分析了 miR-146a 在 SLE 和一系列促炎细胞因子(IL-1、IL-6、IL-8、IL-17 和 TNF-α)中的表达。监测所有测量参数与疾病临床表现和治疗反应之间的关系。我们的研究人群包括 113 例 SLE 患者和 104 名健康志愿者。通过定量实时 PCR(RT-qPCR)测量外周血单个核细胞(PBMC)中的 miR-146a 表达。通过酶联免疫吸附试验(ELISA)检测血浆细胞因子(IL-1β、IL-6、IL-8、IL-17 和 TNF-α)的含量。与健康对照组相比,狼疮患者的 miR-146a 表达明显增加(<0.05)。miR-146a 的受试者工作特征曲线(ROC)分析显示,敏感性为 91%,特异性为 70%。与对照组相比,SLE 患者的 IL-1β、IL-6 和 IL-17 细胞因子显著增加(<0.001),而 IL-8 和 TNF-α 显著降低(<0.001)。在疾病活动度严重的 SLE 患者中,miR-146a 和 TNF-α 的表达明显上调。miR-146a 的表达与 IL-6 呈正相关。我们的结果表明,miR-146a 的升高可作为 SLE 患者的标志物。IL-8 和 TNF-α 的减少与 IL-1β、IL-6 和 IL-17 的升高相结合可能反映了 miR-146a 对狼疮炎症的双重调节作用。尽管我们对 miR-146a 在 SLE 中的作用有所了解,但仍需要进一步研究以改善我们的结果。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4ff0/9903020/2083f9322ca0/10.1177_03946320231154998-fig1.jpg

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