Wilms' tumor protein Wt1 regulates the Interleukin-10 (IL-10) gene.
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.
Charité-Universitaetsmedizin Berlin, Institut fuer Vegetative Physiologie, Hessische Straße 3-4, 10115 Berlin, Germany.
Lina K
LK
Sciesielski
Karin M
KM
Kirschner
Holger
H
Scholz
Anja Bondke
AB
Persson
D000818:Animals; D001483:Base Sequence; D001665:Binding Sites; D002460:Cell Line; D005333:Fetus; D005786:Gene Expression Regulation; D006801:Humans; D016753:Interleukin-10 / Q000235:genetics* / Q000378:metabolism; D008099:Liver / Q000378:metabolism; D051379:Mice; D008969:Molecular Sequence Data; D011401:Promoter Regions, Genetic / Q000235:genetics; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D014158:Transcription, Genetic; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology; D025721:WT1 Proteins / Q000235:genetics / Q000276:immunology / Q000378:metabolism*
D012333:RNA, Messenger; D014409:Tumor Necrosis Factor-alpha; D025721:WT1 Proteins; D016753:Interleukin-10