期刊
FEBS LETTERS
卷 584, 期 22, 页码 4665-4671出版社
ELSEVIER SCIENCE BV
DOI: 10.1016/j.febslet.2010.10.045
关键词
Interleukin; Wilms' tumor; Immune response; Transcription factor; Tumor necrosis factor alpha; Promoter regulation
资金
- Kind-Philipp-Stiftung fur Leukamieforschung
- Deutsche Forschungsgemeinschaft [Scho 634/6-1]
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-a (TNF alpha). These results suggest a novel immune regulatory function of Wt1 in controlling IL-10 gene expression. (C) 2010 Federation of European Biochemical Societies. Published by Elsevier B. V. All rights reserved.
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