Interleukin‐1β and microRNA‐146a in an immature rat model and children with mesial temporal lobe epilepsy

Abstract

Summary Purpose: Increasing evidence indicates that neuroinflammation plays a critical role in the pathogenesis of mesial temporal lobe epilepsy (MTLE). The aim of this study was to investigate the dynamic expression of interleukin (IL)–1β as a proinflammatory cytokine and microRNA (miR)‐146a as a posttranscriptional inflammation‐associated microRNA (miRNA) in the hippocampi of an immature rat model and children with MTLE. Methods: To study the expression of IL‐1β and miR‐146a, we performed a reverse transcription polymerase chain reaction, Western blot, and real‐time quantitative PCR on the hippocampi of immature rats at 11 days of age. Expression was monitored in the acute, latent, and chronic stages of disease (2 h and 3 and 8 weeks after induction of lithium‐pilocarpine status epilepticus, respectively), and in control hippocampal tissues corresponding to the same timeframes. Similar expression methods were applied to hippocampi obtained from children with MTLE and normal controls. Key Findings: The expression of IL‐1β and miR‐146a in both children and immature rats with MTLE differs according to the stage of MTLE development. Both IL‐1β and miR‐146a are significantly up‐regulated, but in opposite ways: IL‐1β expression is highest in the acute stage, when expression of miR‐146a is at its lowest level; miR‐146a expression is highest in the latent stage, when IL‐1β expression is at its lowest level. Both IL‐1β and miR‐146a are up‐regulated in the chronic stage, but not as much as in the other stages. Significance: Our study is the first to focus on the expression of miR‐146a in the immature rat model of lithium‐pilocarpine MTLE and in children with MTLE. We have detected that the expression of proinflammatory cytokine IL‐1β and posttranscriptional inflammation‐associated miR‐146a is variable depending on the disease stage. Furthermore, both IL‐1β and miR‐146a are up‐regulated in immature rats and children with MTLE. Our findings elucidate the role of inflammation in the pathogenesis of MTLE in the immature rat model and children. Therefore, modulation of the IL‐1β–miR‐146a axis may be a novel therapeutic target in the treatment of MTLE.

microRNA s (9, 138, 181A, 221, and 222) and mesial temporal lobe epilepsy in developing brains

“…Kan et al (2012) profiled the miRNAs changes in human TLE [17]. Our previous experiments supported the role of inflammation-related miRNAs (miR-146a, -155, -21, and -132) and brain-specific miRNAs (miR-124 and -134) in the pathogenesis of MTLE in immature rat models and children [20,29,30].…”

Immunity and Inflammation in Epilepsy

“…Differential expression of several miRNAs implicated in the regulation of the IL-1R/TLR-signaling pathways, such as miR146a, has been shown in both animal models and human TLE Iyer et al 2012;Omran et al 2012;Gorter et al 2014). These observations suggest the potential for targeting miRNA as strategy for modulating inflammatory pathways in TLE, as well as in different epilepsyassociated glioneuronal lesions (Iyer et al 2012).…”

MicroRNAs as biomarkers in molecular diagnosis of refractory epilepsy

“…Up-regulated miRNAs includes miR-21, miR-23a, miR-23b, miR-24, miR-27a, miR-27b, miR-34a, miR-126, miR-132, miR-140, miR146a, miR-152, miR-210 and miR-212 while downregulated miRNAs includes miR-33, miR-138, miR-139, miR-187, miR-190, miR-218a, miR-301a, miR-551b and miR-935. Among the up-regulated miRNAs only three were mentioned in three human experiments, which are miR-21, miR-132 and miR-146a [30][31][32]. Of note, miR-134 is also an important microRNA that is up-regulated during epilepsy, which is only profiled in one human experiment of Jimenez-Manteos et al [23].…”