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

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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.

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Acknowledgments

This work was kindly supported by the National Natural Science Foundation of China (Nos. 81371434, 81370771, 81301031) and Hunan Provincial Innovation Foundation for Postgraduate (No. 2501–71380100017). The authors thank Dr. Chao Chen for revising the manuscript. We also thank all members of the laboratory for insightful discussions.

Conflict of Interest

The authors declare that there are no conflicts of interest.

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Authors and Affiliations

  1. Department of Pediatrics, Xiangya Hospital of Central South University, No. 87 Xiangya Road, Changsha, Hunan, 410008, China

    Huimin Kong, Fei Yin, Fang He, Ahmed Omran, Linhong Li, Tianhui Wu, Ying Wang & Jing Peng

  2. Hunan Intellectual and Developmental Disabilities Research Center of Children, Hunan, 410008, China

    Fei Yin, Fang He & Jing Peng

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  1. Huimin Kong
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  2. Fei Yin
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  3. Fang He
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  5. Linhong Li
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Correspondence to Jing Peng.

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Kong, H., Yin, F., He, F. et al. The Effect of miR-132, miR-146a, and miR-155 on MRP8/TLR4-Induced Astrocyte-Related Inflammation. J Mol Neurosci 57, 28–37 (2015). https://doi.org/10.1007/s12031-015-0574-x

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