摘要
目的探讨IL-17参与急性神经炎症的神经保护作用与机制。方法用光感受器间维生素A类结合蛋白(interphotoreceptor retinoid binding protein,IRBP)免疫纯系Lewis大鼠,建立急性-单向型实验性自身免疫性葡萄膜炎(experimental autoimmune uveitis,EAU)模型。RT-PCR法检测在EAU进展中效应T细胞相关分子的表达,免疫荧光法检测视网膜内胶质纤维酸性蛋白(glial fibrillary acidic portein,GFAP)的表达。以PMA/Ionomycin刺激大鼠外周血单个核细胞产生的炎性上清模拟含高水平IL-17的炎性环境,ELISA法检测IL-17等细胞因子水平,Tunel法检测细胞凋亡。结果 EAU发病过程中视网膜局部呈现含高水平IL-17的炎性环境,其中星型胶质细胞高度活化。以炎性上清刺激可诱发原代培养的小脑神经元大量凋亡,加入活化后星型胶质细胞或上清则使凋亡显著降低。IL-17中和抗体可显著抑制炎性上清对神经元的保护作用。结论急性神经炎症中星型胶质细胞通过分泌IL-17发挥神经保护作用。
The study aims to dissect the role of IL-17 in acute neuroinflammation. A monophasie EAU model setup in Lewis rats with immunization of interphotoreceptor retinoid binding protein (IRBP). Then RT-PCR and immunoiluorescenee assays were used to detect effeetor T cell related molecules expression and glial fibrillary acidic protein (GFAP) expression. We observed significantly higher levels of IL-17, IFN-γ etc. in the retina of EAU rats during disease, as compared with control group. Moreover, GFAP+ astrocytes were highly activated during EAU. Furthermore, we obtained an inflammatory medium (Inf. Med.) from the supernatant of Wister rats PBMC with 6 h-PMA/ionomycin stimulation, which contained a high level of IL-17. Whereas co-culture with Inf. Med. resulted in significant apoptosis of the neurons, while supernatant of the stimulated astrocytes showed significant protective effect against the apoptosis. Anti-IL-17 neutralizing Ab could undermine the protection. In conclusion, IL-17 secreted by reactive astrocytes attains significant neuroprotection during acute neuroinflammation.
出处
《免疫学杂志》
CAS
CSCD
北大核心
2015年第7期553-556,共4页
Immunological Journal
基金
齐齐哈尔市科技局社会发展项目(SFGG-201209)