NZB/W狼疮鼠体外IFN-α信号调控网络研究

Comparative analysis of ex vivo ISG expression patterns between NZB/W and BALB/c mice

通过IFN-α刺激基因(ISG)表达谱勾画SLE发病机制中可能的IFN-α异常调控通路。采用基因芯片技术,比较分析发病前新西兰黑/白(NZB/W)F1代狼疮鼠和年龄性别相匹配的对照组BALB/c小鼠脾脏单个核细胞3 h干扰素刺激基因表达谱,并运用信号通路分析软件(CRSD)解析IFN-α信号调控网络。结果:IFN-α体外刺激诱导上调了BALB/c小鼠而非NZB/W狼疮鼠脾脏单个核细胞p53通路相关基因转录产物的表达;IFN-α共同诱导了NZB/W狼疮鼠和BALB/c小鼠Th1型细胞因子和趋化因子网络,相对于BALB/c鼠,IFN-α刺激后IL15、IP10、XCL1、CCL3、CCL7及CCL12的转录产物在NZB/W狼疮鼠中高表达(P值均<0.01)。NZB/W狼疮鼠对IFN-α抑制细胞增殖作用和促炎作用的异常反应,参与并加重了NZB/W狼疮鼠自身免疫性疾病的进展。

To investigate the immune regulatory pathways in the pathogenesis of systemic lupus erythematosus regulated by ex vivo IFN-α stimulation,microarray was employed and the global gene expression patterns in pre-autoimmune NZB/W and BALB/c derived splenic mononuclear cells following ex vivo IFN-α stimulation were analyzed.Global analysis of the gene expression patterns revealed that a set of genes associated with the p53 signal transduction pathway were upregulated in BALB/c but not in NZB/W mice.Of a set of IF...