The Effect of miR-132, miR-146a, and miR-155 on MRP8/TLR4-Induced Astrocyte-Related Inflammation

Abstract

Astrocyte activation, associated with the release of pro-inflammatory cytokines interleukin 1-β (IL-1β), interleukin-6 (IL-6), and tumor necrosis factor alpha (TNF-α), is a hallmark of multiple brain diseases, including mesial temporal lobe epilepsy. In recent years, several microRNAs have emerged as important controllers of Toll-like receptor (TLR) signaling. In this study, we investigated the effect of miR-132, miR-146a, and miR-155 on myeloid-related protein-8 (MRP8) induced astrocyte-related inflammation. Using quantitative polymerase chain reaction (qPCR) and western blot, we found clear upregulation of TLR4 and downstream inflammatory cytokines, along with dysregulation of miR-132, miR-146a, and miR-155 in in vitro astrocytes after exposing them to different concentrations of MRP8. In addition, we focused on the effect of miR-132 on astrocyte-related inflammation induced by MRP8 via lentiviral infection then evaluated the expression of its possible target genes: acetylcholinesterase (AChE) and interleukin-1 receptor-associated kinase (IRAK4). Our results show that miR-132 is a negative feedback regulator of IL-1β and IL-6, but not TNF-α, by targeting IRAK4. Together, our findings demonstrate the novel role of TLR4-related microRNAs, especially miR-132, in the regulation of MRP8-induced astrocyte activation and highlight the importance of miR-132 in the modulation of innate immune response induced by endogenous ligands in neurological diseases.

MicroRNA-132 Interact with p250GAP/Cdc42 Pathway in the Hippocampal Neuronal Culture Model of Acquired Epilepsy and Associated with Epileptogenesis Process

“…MicroRNA-132 (miR-132) is significantly upregulated during active synaptogenesis and plays important roles in spine formation and maturation [2–5]. miR-132 also regulates the inflammatory response and neuronal apoptosis after acute brain injury [6–8]. Several studies have shown that miR-132 is persistently upregulated during epileptogenesis after acute brain injury [9–13].…”

Induction of Multiple miR-200/182 Members in the Brains of Mice Are Associated with Acute Herpes Simplex Virus 1 Encephalitis

“…We showed in Fig A in S1 File that HSVE in our mouse model was associated with astrocytosis and the role of astrocytes in infectious disease in the brain is a relatively unexplored avenue for further research. MiR-146a and miR-155 have both been shown to play roles in astrocyte-mediated neuroinflammation [64]. In addition miR-141 is expressed in normal human astrocytes and the role for this miRNA in these cells, and other members of miR-200 family and miR-182 cluster, has not yet been investigated [65].…”

Comparative study of joint bioinformatics analysis of underlying potential of ‘neurimmiR’, miR-212-3P/miR-132-3P, being involved in epilepsy and its emerging role in human cancer

“…miR-212-3p and miR-132-3p work synergistically to control Sox11 expression in the setting of epilepsy [22]. miR-132 play a negative feedback regulator of IL-1β and IL-6 by targeting IRAK4 in astrocyte-related inflammation induced by MRP8 [23] and promotes epileptogenesis by modulating BDNF/TrkB and p250GAP/Cdc42 signaling in the hippocampal neuronal culture model [24, 25]. Figure 3B…”

“…What is important is IRAK4, a genes associated with epilepsy [23], presented correlation with both miRs and whose dysregulation significantly related to poor survival in several human cancer. Apart from the somatic mutations of IRAK4 itself, all indicated miRs may target single gene to interfere the process of cancer and epilepsy.…”