Abstract
Neuroinflammation is critical in the pathogenesis of neurological diseases. Microglial pro-inflammatory (M1) and anti-inflammatory (M2) status determines the outcome of neuroinflammation. Dexmedetomidine exerts anti-inflammatory effects in many neurological conditions. Whether dexmedetomidine functions via modulation of microglia M1/M2 polarization remains to be fully elucidated. In the present study, we investigated the anti-inflammatory effects of dexmedetomidine on the neuroinflammatory cell model and explored the potential mechanism. BV2 cells were stimulated with LPS to establish a neuroinflammatory model. The cell viability was determined with MTT assay. NO levels were assessed using a NO detection kit. The protein levels of IL-10, TNF-α, iNOS, CD206, ERK1/2, and pERK1/2 were quantified using Western blotting. LPS significantly increased pro-inflammatory factors TNF-α and NO, and M1 phenotypic marker iNOS, and decreased anti-inflammatory factor IL-10 and M2 phenotypic marker CD206 in BV2 cells. Furthermore, exposure of BV2 cells to LPS significantly raised pERK1/2 expression. Pretreatment with dexmedetomidine attenuated LPS-elicited changes in p-ERK, iNOS, TNF-α, NO, CD206 and IL-10 levels in BV2 cells. However, co-treatment with dexmedetomidine and LM22B-10, an agonist of ERK, reversed dexmedetomidine-elicited changes in p-ERK, iNOS, TNF-α, NO, CD206 and IL-10 levels in LPS-exposed BV2 cells. We, for the first time, showed that dexmedetomidine increases microglial M2 polarization by inhibiting phosphorylation of ERK1/2, by which it exerts anti-inflammatory effects in BV2 cells.
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Abbreviations
- CNS:
-
Central nervous system
- AD:
-
Alzheimer’s disease
- PD:
-
Parkinson’s disease
- ALS:
-
Amyotrophic lateral sclerosis
- TBI:
-
Traumatic brain injury
- POCD:
-
Postoperative cognitive dysfunction
- POD:
-
Postoperative delirium
- MAPKs:
-
Mitogen-activated protein kinases
- ERK1/2:
-
Extracellular signal-regulated protein kinase 1/2
- NO:
-
Nitric oxide
- Dex:
-
Dexmedetomidine
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Acknowledgements
This work was supported by the National Natural Science Foundation of China (81071071, 81171247), Key Science and Technology Innovation Team of Shaanxi Province (2014KCT-22) and Science and Technology Development Project of Shaanxi Province Grants (2013KTCL03-09). We would also like to thank Prof. Malgorzata Garstka for langue correction.
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Qiu, Z., Lu, P., Wang, K. et al. Dexmedetomidine Inhibits Neuroinflammation by Altering Microglial M1/M2 Polarization Through MAPK/ERK Pathway. Neurochem Res 45, 345–353 (2020). https://doi.org/10.1007/s11064-019-02922-1
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DOI: https://doi.org/10.1007/s11064-019-02922-1