CHPG通过调控mGluR5表达及JNK信号通路抑制LPS诱导的小胶质细胞激活

CHPG protects against LPS-induced inflammation by modulating mGluR5 and JNK signaling pathway

摘要: 目的探讨激活mGluR5为什么能够抑制激活小胶质细胞诱导的炎症反应. 方法在正常的和基因敲减mGluR5的小胶质细胞中,用脂多糖(LPS)建立炎症模型,通过Griess实验、酶联免疫吸附试验、免疫印迹法、流式细胞术等方法,探测CHPG对LPS诱导的炎症反应,mGluR5表达及其下游MAPKs信号分子活性的影响. 结果 LPS诱导炎症反应,引起mGluR5表达量下降,下游JNK活性下降,CHPG逆转上述过程(P=0.0003, P=0.005).在mGluR5敲减的细胞中,CHPG作用消失(P=0.4694, P=0.4407). 结论激活mGluR5抑制炎症反应是通过上调该受体表达量及其下游的JNK信号通路实现的.

Abstract: Objective To investigate the mechanism by which mGluR5 activation suppress the inflammation induced by activated microglia. Methods The effect of (RS)-2-chloro-5-hydroxyphenylglycine (CHPG) on LPS-induced inflammation, the expression of mGluR5 and its downstream MAPK signaling pathways were detected with Griess test, enzyme-linked immunosorbent assay, western blot and flow cytometry. Results CHPG reversed LPS-induced decrease of mGluR5 (P=0.0003) and p-JNK expression (P=0.005) and no such effect of CHPG was observed in mGluR5 knockdown cells (P=0.4694, P=0.4407). Conclusion The anti-inflammation effect of mGluR5 activation is mediated by raising the expression of mGluR5 and its downstream JNK signaling pathway.