Propofol Attenuates Inflammatory Response In LPS-activated Microglia By Regulating The MiR-155/SOCS1 Pathway

Objective:To investigate the effect of propofol on inflammatory mediator expression and the potential molecular mechanism in LPS-activated BV₂ microglia.Methods:1.To explore the effects of propofol on LPS-induced microglial activation,BV₂ cells were stimulated with LPS?10ng/ml?and treated with various concentrations of propofol?12.5-100?M?for 24h.The expression of NO,TNF-?and IL-6 were measured by the use of Griess and ELISA respectively.2.To assess the role of miR-155 in the anti-inflammatory action of propofol,BV₂cells were stimulated with LPS?10ng/ml?and treated with various concentrations of propofol?12.5-100?M?for 24h,then the expression of miR-155 on LPS stimulation was measured by using a real-time PCR assay.BV₂ microglia cells were incubated with miR-155 hairpin inhibitor and the knockdown was assessed by real-time PCR,then the miR-155 knockdown cells were stimulated with LPS?10ng/ml?and treated with propofol?50?M?.Then the levels of NO,TNF-?and IL-6 were measured after24h.3.To further evaluate whether the miR-155/SOCS1 signaling pathway plays a role in the protective effects of propofol in LPS-induced neuroinflammation.The miR-155knockdown BV₂ cells were treated with LPS?10ng/ml?and propofol?100?M?for 24h and the expression of SOCS1 were measured by Western blot.Then the SOCS1 siRNA was used to knockdown SOCS1 in BV₂ microglia cells and the knockdown was assessed by Western blot.The NO and cytokine levels were measured in SOCS1knockdown cells after treating with LPS?10ng/ml?and propofol?100?M?for 24h.Results:1.Propofol potently decreased the pro-inflammatory mediators,such as NO,TNF-?,and IL-6,at both the transcriptional and translational levels.2.Propofol suppressed the expression of miR-155 in LPS-activated BV₂ microglia cells.Knockdown of miR-155 attenuated the anti-inflammatory effect of propofol in cells after LPS exposure.3.Propofol treatment reduced the LPS-stimulated NO,TNF-?and IL-6 release via upregulating the SOCS1,but it hardly decreased the NO and cytokine levels inSOCS1 knockdown cells.Conclusion:Propofol can suppress the neuro-inflammatory response to LPS in microglia through the regulation of miR-155/SOCS1 pathway.