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

基础医学与临床 ›› 2020, Vol. 40 ›› Issue (2): 145-150.

• 研究论文 • 下一篇

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

顾胜龙¹, 李明星¹, 应苗法¹, 方三华², 饶跃峰^3*, 赵蕊^1*

1.浙江大学医学院附属邵逸夫医院药剂科, 浙江杭州 310016;
2.浙江大学医学院公共技术平台,浙江杭州 310058;
3.浙江大学医学院附属第一医院药剂科, 浙江杭州 310003

收稿日期:2019-03-22 修回日期:2019-07-04 出版日期:2020-02-05 发布日期:2020-02-05
通讯作者: ^*3201039@zju.edu.cn;raoyf@zju.edu.cn
基金资助:
国家自然科学基金 (81872213); 浙江省自然科学基金(LYY19H310010); 浙江省公益技术应用研究计划 (2016C33131)

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

GU Sheng-long¹, LI Ming-xing¹, YING Miao-fa¹, FANG San-hua², RAO Yue-feng^3*, ZHAO Rui^1*

1. Department of Pharmacy, Sir Run Run Shaw Hospital, School of Medicine, Zhejiang University, Hangzhou 310016;
2. Core Facilities, School of Medicine, Zhejiang University,Hangzhou 310058;
3. Department of Pharmacy, the first Affiliated Hospital, Zhejiang University, Hangzhou 310003, China

Received:2019-03-22 Revised:2019-07-04 Online:2020-02-05 Published:2020-02-05
Contact: ^*3201039@zju.edu.cn;raoyf@zju.edu.cn

摘要/Abstract

摘要： 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1 μmol/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。

关键词: CysLT2受体, HAMI3379, 炎性反应, PKCα/NF-κB信号通路

Abstract: 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 1 μmol/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-α and 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-1β and TNF-α was significantly increased and the secretion of IL-10 was obviously reduced in cell supernatant(P＜0.05). The expression of PKCα, IKBα and 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.

Key words: CysLT2 receptor, HAMI3379, inflammation, PKCα/NF-κB signaling pathway

中图分类号:

R966

顾胜龙, 李明星, 应苗法, 方三华, 饶跃峰, 赵蕊. 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[J]. 基础医学与临床, 2020, 40(2): 145-150.

GU Sheng-long, LI Ming-xing, YING Miao-fa, FANG San-hua, RAO Yue-feng, ZHAO Rui. CysLT2 receptor antagonist HAMI3379 inhibits LPS-induced inflammation in mice microglia line BV-2[J]. Basic & Clinical Medicine, 2020, 40(2): 145-150.

参考文献

[1]van Sloten TT, Stehouwer CDA.Carotid Stiffness: a novel cerebrovascular disease risk factor[J]. Pulse, 2016, 4: 24-27.
[2]Kostandy BB. The role of glutamate in neuronal ischemic injury: the role of spark in fire[J]. Neurol Sci, 2012, 33: 223-237.
[3]Won SJ, Kim DY, Gwag BJ. Cellular and molecular pathways of ischemic neuronal death[J]. J Biochem Mol Biol, 2002, 35: 67-86.
[4]Patel AR, Ritzel R, Mccullough LD, et al. Microglia and ischemic stroke: a double-edged sword[J]. Int J Physiol Pathophysiol Pharmacol, 2013, 5: 73-90.
[5]Zhao R, Shi W, Zhang Y, et al. Montelukast, a cysteinyl leukotriene receptor-1 antagonist, attenuates chronic brain injury after focal cerebral ischaemia in mice and rats[J]. J Pharm Pharmacol, 2011, 63: 550-557.
[6]Zhang YJ, Zhang L, Ye YL, et al. Cysteinyl leukotriene receptors CysLT1 and CysLT2 are upregulated in acute neuronal injury after focal cerebral ischemia in mice[J]. Acta Pharmacol Sin, 2006, 27: 1553-1560.
[7]Chen L, Yang Y, Li C, et al. CysLT2 receptor mediates lipopolysaccharide-induced microglial inflammation and consequent neurotoxicity in vitro[J]. Brain Res, 2015, 1624: 433-445.
[8]Lee R Lee M, Wu C, et al. Cerebral ischemia and neuroregeneration[J]. Neural Regen Res, 2018, 13: 373-385.
[9]Uchino H, Morota S, Hirabayashi G, et al. Molecular mechanism of ischemic brain injuries and perspectives of drug therapies for neuroprotection[J]. Masui, 2007, 56: 248-270.
[10]Xiang B, Xiao C, Shen T, et al. Anti-inflammatory effects of anisalcohol on lipopolysaccharide-stimulated BV2 microglia via selective modulation of microglia polarization and down-regulation of NF-κB p65 and JNK activation[J]. Mol Immunol, 2018, 95: 39-46.
[11]Huang X, Zhang W, Li C, et al. Activation of CysLT receptors induces astrocyte proliferation and death after oxygen-glucose deprivation[J]. Glia, 2008, 56: 27-37.
[12]Shi QJ, Wang H, Liu ZX, et al. HAMI 3379, a CysLT2R antagonist, dose- and time-dependently attenuates brain injury and inhibits microglial inflammation after focal cerebral ischemia in rats[J]. Neuroscience, 2015, 291: 53-69.

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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

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

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