结核杆菌诱导人巨噬细胞肿瘤坏死因子受体相关信号传导元件的表达谱  

Comparative differential expression of tumor necrosis factor receptors relating signaling system in macrophages infected with Mycobacterium tuberculosis

作　　者：谢建平[1] 李瑶[1] 乐军[1] 徐永忠[1] 梁莉[1] 于善谦[1] 王洪海[1] 

机构地区：[1]复旦大学遗传所,遗传工程国家重点实验室,上海200433

出　　处：《中华传染病杂志》2003年第4期256-259,共4页Chinese Journal of Infectious Diseases

基　　金：国家自然科学基金资助项目 ( 3 0 2 70 0 72 );973年基金资助项目

摘　　要：目的　调查人巨噬细胞肿瘤坏死因子受体 (TNFR)相关信号传导元件在结核分枝杆菌入侵前后的转录水平和变化幅度。方法　利用含有 12 80 0个基因和 192 0 0个基因全长序列或部分序列的基因芯片研究结核分枝杆菌无毒株和有毒株入侵导致的人巨噬细胞U937全基因组在转录水平的表达谱变化的基础上 ,然后 ,在Northern验证的基础上 ,通过生物信息学分析TNFR相关信号传导元件的表达。结果　结核分枝杆菌无毒株入侵导致的人巨噬细胞U937中与TNFR有关的表达变化不如有毒株的明显 ,TNFR被抑制 ,与TNFR相关的下游基因的表达没有检测到。有毒株导致的变化比较明显 ,MAP激酶 ,NF kappaB ,caspase ,p5 3途径等下游元件的表达分别提高 2～ 3倍 ,内源TNF表达上升 2～ 4倍 ,TNF的转换酶disintegrin金属蛋白酶表达上升 2倍。 结论　TNFR相关的信号传导途径元件参与了宿主对细菌的免疫反应 ,这些基因在转录水平被调控。结核分枝杆菌有毒株比无毒株激发的基因表达变化大。造成这种差异的原因有待进一步分析。Objective To assess the relative transcriptional level of tumor necrosis factor receptor related genes before and after the Mycobacterium tuberculosis invasion. Methods The alteration which occur in gene expression in the cell line U937, following infection with Mycobacterium tuberculosis is investigated. The study was conducted at the transcriptional level, using microarrays consisting of 12 800 and 19 200 human genes respectively. Northern confirmation and bioinformatics analysis are employed. Results Virulent strain leads to more profound changes than the avirulent strain after invasion. The TNFR was both inhibited nearly at the same level. Endogenous TNF was elevated 2 fold by the virulent strain, while no change detected in the avirulent strains. The downstream elements such as MAPK, NF kappa B, p53 related signaling are up regulated 2 4 fold. Also uplift is the TNF converting enzyme, disintegrin metalloproteinase, up to 4.7 folds. Conclusions TNFR participate in the immune response to Mycobacterium tuberculosis infection during the early stage. Virulent strain elicit more profound change than the avirulent ones. The causes for the difference needs further scrutinizing.

关 键 词：结核杆菌 巨噬细胞 肿瘤坏死因子受体 信号传导 结核病 生物信息学 

分 类 号：R346[医药卫生—基础医学]