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  • Transcription factor Tfec contributes to the IL-4-inducible expression of a small group of genes in mouse macrophages including the granulocyte colony-stimulating factor receptor.

    Author(s)
    Rehli, Michael
    Sulzbacher, Sabine
    Pape, Sabine
    Ravasi, Timothy
    A. Wells, Christine
    Heinz, Sven
    Sollner, Liane
    Chartouni, Carol
    W. Krause, Stefan
    Steingrimsson, Eirikur
    A. Hume, David
    Andreesen, Reinhard
    Griffith University Author(s)
    Wells, Christine
    Year published
    2005
    Metadata
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    Abstract
    Expression of the mouse transcription factor EC (Tfec) is restricted to the myeloid compartment, suggesting a function for Tfec in the development or function of these cells. However, mice lacking Tfec develop normally, indicating a redundant role for Tfec in myeloid cell development. We now report that Tfec is specifically induced in bone marrow-derived macrophages upon stimulation with the Th2 cytokines, IL-4 and IL-13, or LPS. LPS induced a rapid and transient up-regulation of Tfec mRNA expression and promoter activity, which was dependent on a functional NF-kappaB site. IL-4, however, induced a rapid, but long-lasting, ...
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    Expression of the mouse transcription factor EC (Tfec) is restricted to the myeloid compartment, suggesting a function for Tfec in the development or function of these cells. However, mice lacking Tfec develop normally, indicating a redundant role for Tfec in myeloid cell development. We now report that Tfec is specifically induced in bone marrow-derived macrophages upon stimulation with the Th2 cytokines, IL-4 and IL-13, or LPS. LPS induced a rapid and transient up-regulation of Tfec mRNA expression and promoter activity, which was dependent on a functional NF-kappaB site. IL-4, however, induced a rapid, but long-lasting, increase in Tfec mRNA, which, in contrast to LPS stimulation, also resulted in detectable levels of Tfec protein. IL-4-induced transcription of Tfec was absent in macrophages lacking Stat6, and its promoter depended on two functional Stat6-binding sites. A global comparison of IL-4-induced genes in both wild-type and Tfec mutant macrophages revealed a surprisingly mild phenotype with only a few genes affected by Tfec deficiency. These included the G-CSFR (Csf3r) gene that was strongly up-regulated by IL-4 in wild-type macrophages and, to a lesser extent, in Tfec mutant macrophages. Our study also provides a general definition of the transcriptome in alternatively activated mouse macrophages and identifies a large number of novel genes characterizing this cell type.
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    Journal Title
    Journal of Immunology
    Volume
    174
    Issue
    11
    Publisher URI
    http://www.jimmunol.org/
    Copyright Statement
    © 2003 AAI. Self-archiving of the author-manuscript version in open access institutional repository is not yet supported by this publisher. Please refer to the journal link for access to the definitive, published version or contact the author for more information.
    Subject
    Immunology
    Publication URI
    http://hdl.handle.net/10072/20922
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