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.
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Previous reports showed miR-132 was also expressed in pericytes and glial cells.
“However, previous reports showed that miR-132 was also expressed in pericytes and glial cells43,44.”
From Neurons secrete miR-132-containing exosomes to regulate brain vascular integrity (2017) · cites this paper as [44]
Cites
Widespread changes in protein synthesis induced by microRNAs
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“homologous sequence, each miRNA has the potential to regulate the translation of hundreds of genes (Selbach et al. 2008).”
BackgroundPhysiology and immunology of the cholinergic antiinflammatory pathway
Tracey, K. J. (2007) · Journal of Clinical Investigation · doi:10.1172/jci30555 · Cited by 1,563 · cited 1× · see citing works
“This enzyme limits the level of acetylcholine (ACh), an important inhibitor of peripheral inflammation and one of the characterized mediators of Bcholinergic antiinflammatory pathway^ (Tracey 2007).”
BackgroundVogl, T., Tenbrock, K., Ludwig, S., Leukert, N., Ehrhardt, C., van Zoelen, M. A. D., Nacken, W., Foell, D., van der Poll, T., Sorg, C., et al. (2007) · Nature Medicine · doi:10.1038/nm1638 · Cited by 1,418 · cited 2× · see citing works
“Although MRP8 always presents as a heterocomplex together with MRP14 (Floris et al. 2004; Viemann et al. 2007; Vogl et al. 2004), it has been argued that MRP8 is the active component that binds to the receptor site (Vogl et al. 2007; Yonekawa et al. 2011).”
BackgroundLinking oxidative stress to inflammation: Toll-like receptors
Gill, R., Tsung, A., & Billiar, T. (2010) · Free Radical Biology and Medicine · doi:10.1016/j.freeradbiomed.2010.01.006 · Cited by 553 · see citing works
MicroRNA-146a: A Key Regulator of Astrocyte-Mediated Inflammatory Response
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Neurons secrete miR-132-containing exosomes to regulate brain vascular integrity
Xu, B., Zhang, Y., Du, X.-F., Li, J., Zi, H.-X., Bu, J.-W., Yan, Y., Han, H., & Du, J.-L. (2017) · Cell Research · doi:10.1038/cr.2017.62 · Cited by 354 · see citing works
- Authors
- Kong, H., Yin, F., He, F., Omran, A., Li, L., Wu, T., Wang, Y., & Peng, J.
- Venue
- Journal of Molecular Neuroscience
- Published
- 2015-05-10
- Volume
- 57
- Issue
- 1
- Pages
- 28-37
- ISSN
- 0895-8696
- 1559-1166
- Cited by
- 70
- References
- 5
- Language
- en
- Licence
- www.springer.com/tdm (tdm)
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