摘要
目的研究结核分枝杆菌早期分泌抗原CFP-10-ES-AT-6复合物(CE复合物)对人单核-巨噬细胞功能表型的影响及其作用的细胞信号传导通路。方法分别采用ELISA法以及流式细胞仪检测大肠杆菌克隆表达纯化的CE复合物在不同时间及浓度对人单核-巨噬细胞TNF-α产生对细胞表型的影响,并且应用各种细胞信号传导通路抑制剂来探讨CE复合物作用的细胞信号传导通路。结果结核分枝杆菌CE复合物能够在早期(6~8h)诱导人单核-巨噬细胞活化,大量产生TNF-α,但在晚期(〉48h),则没有此作用;细胞信号传导通路MEK1/2和p38 MAPK的选择性抑制剂SB203580、PD98059、U0126能抑制CE的这种作用;CE复合物在早期(18h)促进单核-巨噬细胞表面抗原提呈功能分子CD80、CD40的表达。结论CE复合物在感染早期可能通过激活MEK1/2和p38MAPK刺激单核巨噬细胞活化,但在晚期则没有此作用。在感染早期可能具有重要的抗结核保护作用。
Objective To study the effect of mycobacterium tuberculosis early secretory antigen CFP-10-ESAT-6 complex (CE complex) on the function and phenotype of monocytes/macrophage and signaling pathway. Methods Human monocytes or macrophages were treated with recombinant CE complex at different culture periods or dose. Supernatants was collected for TNF-α detection by ELISA and flow cytometry. Signaling pathway inhibitors was used to find the signaling pathway of CE complex. Results Mycobacterium tuberculosis CE complex induced monocytes/macrophage activation,formation of a large number of TNF-α in the early period(6-8 h) ,but not in later ( 〉48 h) ; Selective signaling pathway inhibitors of MEK1/2 and p38 MAPK such as SB203580, PD9805, and U0126 could inhibit it. CE complex also promoted monocytes/macrophage cell surface molecules CD80 and CD40 expression in the early period(〈 18 h). Conclusion CE complex may induce monocytes/macrophages 'activation by MEK1/2 and p38 MAPK, but not in later. This may have important significance for protection in the early period of infection.
出处
《安徽医科大学学报》
CAS
北大核心
2008年第2期124-127,共4页
Acta Universitatis Medicinalis Anhui
基金
安徽省自然科学基金(编号:050430706)
安徽省教育厅自然科学基金(编号:KJ2007B196)
上海市科委基金项目(编号:06DZ22034和064119648)
关键词
分枝杆菌
结核
肿瘤坏死因子-Α
mycobacterium tuberculosis
tumor necrosis factor alpha