Propofol inhibition of microglial inflammatory processes through the toll-like receptor 4-p38 mitogen-activated protein kinase signaling pathway

We investigated the effects of propofol on inflammatory processes induced by lipopolysaccharide (LPS)-treated microglia and elucidated the role of the toll-like receptor 4 (TLR4)-p38 mitogen-activated protein kinase (MAPK) pathway in such effects. First, BV-2 microglia were divided into control, propofol (30 mu M), LPS (1 mu g/mL), and LPS+ propofol (1 mu g/mL LPS+ 30 mu M propofol) groups. Then, enzyme-linked immunosorbent assay (ELISA) and MTT, polymerase chain reaction (PCR), and western blot assays were utilized to determine cell viability, inflammatory factors in the cell culture supernatant, and the expression of essential proteins in the TLR4-p38 MAPK inflammatory pathway. Microglial activation was significantly stronger in the LPS and LPS+ propofol groups than in the control and propofol groups (P < 0.05). The microglial cell viability was higher in the LPS+ propofol group than it was in the LPS group (P < 0.05). The interleukin (IL)-1 beta, IL-6, and tumor necrosis factor (TNF)-alpha levels were higher in culture supernatant from the LPS and LPS+ propofol groups than they were in the control and propofol groups; the IL-1 beta, IL-6, and TNF-alpha levels were lower in the supernatant medium from the LPS+ propofol group than they were in the LPS group (P < 0.05). PCR and western blot results showed that microglial p38MAPK and TLR4 mRNA and protein expression was significantly higher in the LPS and LPS+ propofol groups than in the control and propofol groups (P < 0.05). Microglial p38 MAPK and TLR4 mRNA and protein expression was significantly lower in the LPS+ propofol group than in the LPS group (P < 0.05). Thus, our results indicated that propofol inhibits microglial activation and inflammatory reactions by possibly downregulating the TLR4-p38 MAPK signaling pathway.