MicroRNA-101 targets MAPK phosphatase-1 to regulate the activation of MAPKs in macrophages
Abstract
MAPK phosphatase-1 (MKP-1) is an archetypical member of the dual-specificity phosphatase family that deactivates MAPKs. Induction of MKP-1 has been implicated in attenuating the LPS- or peptidoglycan-induced biosynthesis of proinflammatory cytokines, but the role of noncoding RNA in the expression of the MKP-1 is still poorly understood. In this study, we show that MKP-1 is a direct target of microRNA-101 (miR-101). Transfection of miR-101 attenuates induction of MKP-1 by LPS as well as prolonged activation of p38 and JNK/stress-activated protein kinase, whereas inhibition of miR-101 enhances the expression of MKP-1 and shortens p38 and JNK activation. We also found that expression of miR-101 is induced by multiple TLR ligands, including LPS, peptidoglycan, or polyinosinic-polycytidylic acid, and that inhibition of PI3K/Akt by LY294002 or Akt RNA interference blocks the induction of miR-101 by LPS in RAW264.7 macrophage cells. Moreover, treatment of cells with dexamethasone, a widely used anti-inflammatory agent, markedly inhibits miR-101 expression and enhances the expression of MKP-1 in LPS-stimulated macrophages. Together, these results indicate that miR-101 regulates the innate immune responses of macrophages to LPS through targeting MKP-1.
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miR-101 and miR-142-3p are expressed in peripheral macrophages, but their functions in microglia remain unknown.
“are expressed in peripheral macrophages, but their functions in microglia remain unknown (Zhu et al., 2010; Xie et al., 2014).”
From miR-142-3p Regulates BDNF Expression in Activated Rodent Microglia Through Its Target CAMK2A (2020) · cites this paper as Zhu et al., 2010
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The Kinase Akt1 Controls Macrophage Response to Lipopolysaccharide by Regulating MicroRNAs
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MAP kinase phosphatase 1 controls innate immune responses and suppresses endotoxic shock
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“MKP-1 expression itself is induced rapidly by stimulation with LPS and other microbial components, leading to feedback control of deactivation of MAPKs (17).”
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Huang, C.-Y., & Tan, T.-H. (2012) · Cell & Bioscience · doi:10.1186/2045-3701-2-24 · Cited by 260 · see citing works
MicroRNAs: New Regulators of Toll-Like Receptor Signalling Pathways
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miR-15a/16 Regulates Macrophage Phagocytosis after Bacterial Infection
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miR-142-3p Regulates BDNF Expression in Activated Rodent Microglia Through Its Target CAMK2A
Gupta, N., Jadhav, S., Tan, K.-L., Saw, G., Mallilankaraman, K. B., & Dheen, S. T. (2020) · Frontiers in Cellular Neuroscience · doi:10.3389/fncel.2020.00132 · Cited by 40 · see citing works
- Authors
- Zhu, Q.-Y., Liu, Q., Chen, J.-X., Lan, K., & Ge, B.-X.
- Affiliations
- Institute Pasteur of Shanghai, Chinese Academy of Sciences , Shanghai ,
- The Key Laboratory of Stem Cell Biology, Institute of Health Sciences, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences/Shanghai Jiao Tong University School of Medicine , Shanghai ,
- Venue
- The Journal of Immunology
- Publisher
- Oxford University Press (OUP)
- Published
- 2010-12
- Volume
- 185
- Issue
- 12
- Pages
- 7435-7442
- ISSN
- 0022-1767
- 1550-6606
- Cited by
- 137
- References
- 4
- Language
- en
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