IgG刺激诱发的小胶质细胞Toll样受体4表达及细胞因子分泌  

Toll-like receptor 4 expression and cytokine secretion in microglial cells induced by IgG stimulation

作　　者：吴瑞[1,2] 刘玲[2] 彭正午[2] 段小莉[2] 王百忍[2] 靳亚平[1] 邝芳[2] 

机构地区：[1]西北农林科技大学动物医学院,陕西杨凌712100 [2]第四军医大学神经科学研究所,陕西西安710032

出　　处：《细胞与分子免疫学杂志》2009年第3期201-203,207,共4页Chinese Journal of Cellular and Molecular Immunology

基　　金：国家自然科学基金资助项目(30500451)

摘　　要：目的:了解在体外培养条件下免疫球蛋白G(IgG)刺激对小胶质细胞表达Toll样受体4(TLR4)和分泌细胞因子的作用。方法:用不同浓度的IgG(2mg/L、20mg/L、200mg/L)及脂多糖(LPS)(10mg/L)刺激原代培养的大鼠小胶质细胞,24h后以免疫荧光染色观察TLR4的表达,ELISA法检测培养上清中肿瘤坏死因子α(TNF-α)和γ干扰素(IFN-γ)的含量。结果:IgG直接作用于体外培养的小胶质细胞后,以剂量依赖的方式引起TLR4的表达和TNF-α的分泌,但未检测到IFN-γ含量的变化。作为阳性对照的LPS引起了小胶质细胞TLR4表达,并诱导了TNF-α及少量IFN-γ的分泌。结论:同种IgG刺激可使体外培养的小胶质细胞大量表达TLR4,可能通过MyD88依赖途径导致炎性细胞因子分泌。结果提示至少在中枢神经系统的固有免疫反应中,TLR4可能发挥识别病原体之外的蛋白分子,例如IgG的作用。AIM：To investigate the effects of immunoglobulin G（IgG）on the expression of toll-like receptor 4（TLR4）and secretion of cytokines in microglial cells in vitro.METHODS：Cultured primary rat microglial cells were stimulated with different concentrations of rat IgG（2 mg/L,20 mg/L,200 mg/L）and lipopolysaccharide（LPS）10 mg/L for 24 h,respectively.The TLR4 expression in the microglial cells was examined by immunofluorescence staining and tumor necrosis factor-α（TNF-α）and interferon-γ（IFN-γ）levels in the culture medium were assayed by ELISA.RESULTS：IgG stimulation induced a significant TLR4 expression and TNF-α secretion in cultured microglial cells in a dose-dependent manner,while IFN-γ was not detected in the same medium samples.As a positive control,LPS caused increases of TLR4 expression and both IFN-γ and TNF-α production in the microglial cells.CONCLUSION：TLR4 expression could be induced in microglia in vitro by non-pathogenic protein,IgG from the same species.Therefore,congeneric IgG stimulation might lead to proinflammmatory cytokine production,probably via MyD88-dependent pathway.This finding suggests that TLR4 may play more roles than pathogen recognition of innate immune reactivity,at least in the central nervous system.

关 键 词：小胶质细胞 免疫球蛋白G TOLL样受体4 肿瘤坏死因子α Γ干扰素 

分 类 号：R392.12[医药卫生—免疫学]