Yang Min, Zhao Li, Sun Mingyan
Department of Infectious Diseases, Affiliated Hospital of Weifang Medical University, Weifang, Shandong 261031, China.
Department of Infectious Diseases, Yidu Central Hospital of Weifang, Weifang, Shandong 262500, China.
Int J Genomics. 2020 May 13;2020:2198308. doi: 10.1155/2020/2198308. eCollection 2020.
Sepsis is a life-threatening condition and a systemic inflammatory response syndrome (SIRS) driven by infection. This study aimed at investigating the expression of microRNA-103 (miR-103) in sepsis patients, evaluating its diagnostic value, and exploring the regulatory effect of miR-103 on LPS-induced inflammation in monocytes.
Expression of miR-103 was measured using quantitative real-time PCR. A receiver operating characteristics curve was plotted to evaluate the diagnostic vale of miR-103. Serum and cell supernatant levels of proinflammatory cytokines were analyzed using ELISA. The interaction between miR-103 and Toll-like receptors 4 (TLR4) was analyzed using luciferase reporter assay. The effect of miR-103 on inflammation was examined in LPS-treated monocytes.
Serum expression of miR-103 was decreased in noninfectious SIRS and sepsis patients compared with healthy controls, and the lowest expression value was observed in sepsis patients (all < 0.05). Serum levels of miR-103 have considerable diagnostic accuracy in distinguishing sepsis patients from SIRS patients and healthy controls. A negative correlation was found between miR-103 and inflammatory responses in sepsis patients. TLR4 was demonstrated to be a direct target of miR-103 and was negatively regulated by miR-103 in monocytes. The promoted inflammatory responses by LPS in monocytes were reversed by the overexpression of miR-103.
All the data revealed that serum decreased miR-103 in sepsis patients serves as a promising noninvasive diagnostic biomarker and may be involved in the pathogenesis of sepsis by regulating inflammatory responses via targeting TLR4.
脓毒症是一种危及生命的疾病,是由感染驱动的全身炎症反应综合征(SIRS)。本研究旨在调查脓毒症患者中微小RNA-103(miR-103)的表达,评估其诊断价值,并探讨miR-103对脂多糖(LPS)诱导的单核细胞炎症的调节作用。
采用定量实时PCR检测miR-103的表达。绘制受试者工作特征曲线以评估miR-103的诊断价值。使用酶联免疫吸附测定(ELISA)分析促炎细胞因子的血清和细胞上清液水平。使用荧光素酶报告基因检测分析miR-103与Toll样受体4(TLR4)之间的相互作用。在LPS处理的单核细胞中检测miR-103对炎症的影响。
与健康对照相比,非感染性SIRS和脓毒症患者血清中miR-103的表达降低,脓毒症患者中观察到最低表达值(均<0.05)。血清miR-103水平在区分脓毒症患者与SIRS患者和健康对照方面具有相当高的诊断准确性。在脓毒症患者中发现miR-103与炎症反应之间呈负相关。TLR4被证明是miR-103的直接靶标,并且在单核细胞中被miR-103负调节。miR-103的过表达逆转了LPS在单核细胞中促进的炎症反应。
所有数据表明,脓毒症患者血清中miR-103降低是一种有前景的非侵入性诊断生物标志物,可能通过靶向TLR4调节炎症反应而参与脓毒症的发病机制。