Propofol attenuates BV2 microglia inflammation via NMDA receptor inhibition

Activated microglia, involved in the occurrence and improvement of sepsis-associated encephalopathy, can induce the expression of pro-inflammatory cytokines and pro-inflammatory enzymes, resulting in inflammation-mediated neuronal cell death. It was reported that propofol could inhibit lipopolysaccharide (LPS)-induced pro-inflammatory cytokines and pro-inflammatory enzymes expression in BV2 and primary microglial cells. However, the underlying mechanism is not well known. In the present study, we investigated whether and how propofol inhibited LPS-induced the expression of pro-inflammatory cytokines and pro-inflammatory enzymes in BV2 cells. LPS induced pro-inflammatory cytokines and pro-inflammatory enzymes expression, NF-κB, extracellular regulated kinase 1/2 (ERK) and Calcium (Ca2+)/calmodulin-dependent protein kinase II (CaMK II) phosphorylation, and BV2 cells Ca2+ accumulation. Propofol could reverse these effects induced by LPS. MK801, an inhibitor of NMDA receptor, could attenuate LPS-induced Ca2+ accumulation, the expression of pro-inflammatory cytokines and pro-inflammatory enzymes, phosphorylation of NF-κB, ERK and CaMK II, which was similar with propofol. Moreover, these effects of propofol could be counteracted by rapastinel, an activator of NMDA receptor. The present study suggested that propofol, via inhibiting NMDA receptor, attenuating Ca2+ accumulation, inhibiting CaMK II, ERK1/2 and NF-κB phosphorylation, down-regulated LPS-induced pro-inflammatory cytokines and pro-inflammatory enzymes expression.The accepted manuscript in pdf format is listed with the files at the bottom of this page. The presentation of the authors' names and (or) special characters in the title of the manuscript may differ slightly between what is listed on this page and what is listed in the pdf file of the accepted manuscript; that in the pdf file of the accepted manuscript is what was submitted by the author