CysLT2受体拮抗剂HAMI3379抑制LPS诱导小鼠小胶质瘤细胞系的炎性反应

目的探究半胱氨酰白三烯2(CysLT2)受体拮抗剂HAMI3379对LPS诱导小鼠小胶质细胞(BV-2)炎性反应的调控作用及其可能的作用机制。方法体外培养BV-2,将BV-2分为对照组、LPS(100 ng/mL)组、HAMI3379(0.01、0.1和1μmol/mL)组和LPS+HAMI3379组。CCK-8法检测BV-2细胞的增殖;ELISA检测细胞上清液中炎性因子IL-1β、TNF-α、IL-10的含量;Western-blot检测PKCα、IKBα、NF-κB p50和p65蛋白的表达。结果LPS能够激活BV-2细胞,促进其细胞的增殖(P<0.05);显著增加细胞上清液中炎性因子IL-1β、TNF-α的分泌,减少IL-10的分泌(P<0.05);且显著上调PKCα、IKBα、p65蛋白的表达水平(P<0.05)。CysLT2受体拮抗剂HAMI3379能够显著减轻上述变化(P<0.05)。结论CysLT2受体拮抗剂HAMI3379能够抑制LPS激活BV-2细胞,抑制炎性反应,其作用机制可能与抑制PKCα/NF-κB信号通路有关。

CysLT2 receptor antagonist HAMI3379 inhibits LPS-induced inflammation in mice microglia line BV-2

Objective To investigate the role and possible mechanism of CysLT2 receptor antagonist HAMI3379 on the inflammatory response of mouse microglia(BV-2)induced by LPS.Methods BV-2 cells were divided into control group,LPS(100 ng/mL)group,HAMI3379(0.01,0.1 and 1μmol/mL)group and LPS+HAMI3379 group.The proliferation of BV-2 cells was detected by CCK-8 assay.The contents of cytokines IL-1β,TNF-αand IL-10 were measured by ELISA assay.Western blot was used to detect the expression of PKCα,IKBα,NF-κB p50 and p65 protein.Results LPS significantly induced the activation of BV-2 cells and promoted proliferation of cells(P<0.05).The secretion of inflammatory factors IL-1βand TNF-αwas significantly increased and the secretion of IL-10 was obviously reduced in cell supernatant(P<0.05).The expression of PKCα,IKBαand p65 proteins were significantly up-regulated(P<0.05).The CysLT2 receptor antagonist HAMI3379 was able to reduce these changes.Conclusions The CysLT2 receptor antagonist HAMI3379 may inhibit the activation of BV-2 cells induced by LPS and reduce the inflammatory response,and the possible mechanism is related to the inhibition of PKCα/NF-κB signaling pathway.