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Correlation Between IL-10 and microRNA-187 Expression in Epileptic Rat Hippocampus and Patients with Temporal Lobe Epilepsy

机译:癫痫大鼠海马和颞叶癫痫患者IL-10和microRNA-187表达的相关性

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摘要

Accumulating evidence is emerging that microRNAs (miRNAs) are key regulators in controlling neuroinflammatory responses that are known to play a potential role in the pathogenesis of temporal lobe epilepsy (TLE). The aim of the present study was to investigate the dynamic expression pattern of interleukin (IL)-10 as an anti-inflammatory cytokine and miR-187 as a post-transcriptional inflammation-related miRNA in the hippocampus of a rat model of status epilepticus (SE) and patients with TLE. We performed a real-time quantitative PCR and western blot on rat hippocampus 2 h, 7 days, 21 days and 60 days following pilocarpine-induced SE, and on hippocampus obtained from TLE patients and normal controls. To detect the relationship between IL-10 and miR-187 on neurons, lipopolysaccharide (LPS) and IL-10-stimulated neurons were performed. Furthermore, we identified the effect of antagonizing miR-187 by its antagomir on IL-10 secretion. Here, we reported that IL-10 secretion and miR-187 expression levels are inversely correlated after SE. In patients with TLE, the expression of IL-10 was also significantly upregulated, whereas miR-187 expression was significantly downregulated. Moreover, miR-187 expression was significantly reduced following IL-10 stimulation in an IL-10–dependent manner. On the other hand, antagonizing miR-187 promoted the production of IL-10 in hippocampal tissues of rat model of SE. Our findings demonstrate a critical role of miR-187 in the physiological regulation of IL-10 anti-inflammatory responses and elucidate the role of neuroinflammation in the pathogenesis of TLE. Therefore, modulation of the IL-10 / miR-187 axis may be a new therapeutic approach for TLE.
机译:越来越多的证据表明,microRNA(miRNA)是控制神经炎性反应的关键调节剂,已知它们在颞叶癫痫(TLE)的发病机理中具有潜在作用。本研究的目的是研究癫痫持续状态大鼠模型海马中白细胞介素(IL)-10作为抗炎细胞因子和miR-187作为转录后炎症相关miRNA的动态表达模式( SE)和TLE患者。我们在毛果芸香碱诱导的SE后2 h,7天,21天和60天,对从TLE患者和正常对照获得的海马进行了实时定量PCR和Western印迹。为了检测神经元上IL-10和miR-187的关系,进行了脂多糖(LPS)和IL-10刺激的神经元的检测。此外,我们确定了它的antagomir拮抗miR-187对IL-10分泌的作用。在这里,我们报道了SE后IL-10分泌和miR-187表达水平呈负相关。在TLE患者中,IL-10的表达也显着上调,而miR-187的表达则显着下调。此外,在IL-10刺激后,miR-187的表达以IL-10依赖性方式显着降低。另一方面,拮抗miR-187可促进SE大鼠模型海马组织中IL-10的产生。我们的发现证明了miR-187在IL-10抗炎反应的生理调节中的关键作用,并阐明了神经炎症在TLE发病机理中的作用。因此,调节IL-10 / miR-187轴可能是TLE的新治疗方法。

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