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Acta Physiologica 2009; Volume 195, Supplement 669
The 88th Annual Meeting of The German Physiological Society
3/22/2009-3/25/2009
Giessen, Germany
THE WILMS TUMOR SUPPRESSOR WT1 REGULATES INTERLEUKIN-10 EXPRESSION IN MACROPHAGOCYTIC CELLS
Abstract number: P277
Bondke1 A., Kirschner1 K., Scholz1 H.
1Institute of Physiology, Charit Universitaetsmedizin Berlin, Berlin
The Wilms' tumor gene, WT1, encodes a zinc finger transcription factor which functions both as a tumor suppressor and as a key regulator of embryonic development. WT1 is also expressed in hematopoietic progenitor cells and has been implicated in the pathogenesis of acute myeloid leukemia. However, expression of WT1 by mature monocytes/ macrophages and its potential role in immune function has not been studied previously.
In the present study, we show that WT1 is positively deregulated in monocytic cells in response to pro-inflammatory stimulation and enhances interleukin-10 (IL-10) expression. Silencing of WT1 by siRNA transfection of a mesonephric cell line reduced IL-10 mRNA levels (cDNA microarray analysis, real-time RT PCR) by approximately 80% compared to transfection with a non-targeting siRNA. IL-10 transcripts were increased >15-fold in cells inducibly expressing the transcriptionally active WT1(-KTS) protein. In contrast, the WT1(+KTS) protein, which has a role in mRNA processing rather than in transcriptional regulation, did not significantly change IL-10 mRNA levels. Moreover, IL-10 and Wt1 could be detected in monocytes from healthy volunteers. Treatment of murine monocytic J774.1 cells with bacterial lipopolysaccharide (LPS) to activate the innate immune response reaction caused an approx. 5-fold increase in Wt1 mRNA levels, which was accompanied by an enhanced expression of IL-10.
These findings suggest a novel role of WT1 in the regulation of the innate immune response.
To cite this abstract, please use the following information:
Acta Physiologica 2009; Volume 195, Supplement 669 :P277