Wilms' tumor protein Wt1 regulates the Interleukin-10 (IL-10) gene.

Abstract

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.

• Authors: Lina K Sciesielski, Karin M Kirschner, Holger Scholz, Anja Bondke Persson
• Journal: FEBS letters (FEBS Lett) Vol. 584 Issue 22 Pg. 4665-71 (Nov 19 2010) ISSN: 1873-3468 [Electronic] England
• PMID: 20974136 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2010 Federation of European Biochemical Societies. Published by Elsevier B.V. All rights reserved.

Chemical References

• RNA, Messenger
• Tumor Necrosis Factor-alpha
• WT1 Proteins
• Interleukin-10

Topics

• Animals
• Base Sequence
• Binding Sites
• Cell Line
• Fetus
• Gene Expression Regulation
• Humans
• Interleukin-10 (genetics, metabolism)
• Liver (metabolism)
• Mice
• Molecular Sequence Data
• Promoter Regions, Genetic (genetics)
• RNA, Messenger (genetics, metabolism)
• Transcription, Genetic
• Tumor Necrosis Factor-alpha (pharmacology)
• WT1 Proteins (genetics, immunology, metabolism)