Dexmedetomidine Inhibits Neuroinflammation by Altering Microglial M1/M2 Polarization Through MAPK/ERK Pathway.
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.
['Qiu|Zhengguo|Z|', 'Lu|Pan|P|', 'Wang|Kui|K|', 'Zhao|Xijuan|X|', 'Li|Qianqian|Q|', 'Wen|Jieqiong|J|', 'Zhang|Hong|H|', 'Li|Rong|R|', 'Wei|Haidong|H|', 'Lv|Yuying|Y|', 'Zhang|Shuyue|S|', 'Zhang|Pengbo|P|http://orcid.org/0000-0002-4341-9587']
D000818:Animals D000893:Anti-Inflammatory Agents D002461:Cell Line, Transformed D016764:Cell Polarity D020927:Dexmedetomidine D007249:Inflammation D008070:Lipopolysaccharides D020935:MAP Kinase Signaling System D051379:Mice D017628:Microglia D009569:Nitric Oxide
Dexmedetomidine Polarization Microglia Anti-inflammation