Charité-Universitaetsmedizin Berlin, Institut fuer Vegetative Physiologie, Hessische Straße 3-4, 10115 Berlin, Germany.
FEBS Lett. 2010 Nov 19;584(22):4665-71. doi: 10.1016/j.febslet.2010.10.045. Epub 2010 Oct 26.
We identified the Wilms' tumor protein, Wt1, as a novel transcriptional activator of the immunosuppressant cytokine interleukin-10 (IL-10). Silencing of Wt1 by RNA interference reduced IL-10 mRNA levels by approximately 90%. IL-10 transcripts were increased more than 15-fold upon forced expression of Wt1. Electrophoretic mobility shift assay and chromatin immunoprecipitation revealed a cis-element that was responsible for activation of the IL-10 promoter by Wt1 in murine macrophages. Mutation of the Wt1 binding motif abrogated stimulation of the IL-10 promoter by tumor necrosis factor-α (TNFα). These results suggest a novel immune regulatory function of Wt1 in controlling IL-10 gene expression.
我们发现肾母细胞瘤蛋白 WT1 是免疫抑制剂细胞因子白细胞介素 10（IL-10）的新型转录激活因子。通过 RNA 干扰沉默 WT1 可使 IL-10 mRNA 水平降低约 90%。强制表达 WT1 可使 IL-10 转录物增加 15 倍以上。电泳迁移率变动分析和染色质免疫沉淀显示，顺式元件负责 WT1 在鼠巨噬细胞中激活 IL-10 启动子。WT1 结合基序的突变可消除肿瘤坏死因子-α（TNFα）对 IL-10 启动子的刺激。这些结果表明 WT1 在控制 IL-10 基因表达方面具有新的免疫调节功能。
