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Wilms’ tumor protein Wt1 regulates the Interleukin‐10 (IL‐10) gene
Author(s) -
Sciesielski Lina K.,
Kirschner Karin M.,
Scholz Holger,
Persson Anja Bondke
Publication year - 2010
Publication title -
febs letters
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.593
H-Index - 257
eISSN - 1873-3468
pISSN - 0014-5793
DOI - 10.1016/j.febslet.2010.10.045
Subject(s) - microbiology and biotechnology , chromatin immunoprecipitation , electrophoretic mobility shift assay , wilms' tumor , biology , gene silencing , gene knockdown , rna interference , cancer research , gene expression , messenger rna , promoter , tumor necrosis factor alpha , gene , rna , immunology , genetics
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.