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Suppression of Il-12 transcription in macrophages following Fc gamma receptor ligation.

TitleSuppression of Il-12 transcription in macrophages following Fc gamma receptor ligation.
Publication TypeJournal Article
Year of Publication2001
AuthorsM Cappiello G, Sutterwala FS, Trinchieri G, Mosser DM, Ma X
JournalJ Immunol
Volume166
Issue7
Pagination4498-506
Date Published2001 Apr 01
ISSN0022-1767
KeywordsActive Transport, Cell Nucleus, Animals, Binding, Competitive, Cell Line, Cell Nucleus, DNA-Binding Proteins, Down-Regulation, Gene Expression Regulation, Genetic Vectors, Interferon Regulatory Factor-1, Interferon Regulatory Factors, Interferon-gamma, Interleukin-12, Ligands, Macromolecular Substances, Macrophages, Mice, Phosphoproteins, Promoter Regions, Genetic, Protein Binding, Protein Structure, Tertiary, Proto-Oncogene Proteins, Receptors, IgG, Repressor Proteins, Trans-Activators, Transcription Factors, Transcription, Genetic, Transfection
Abstract

Ligating Fc gamma R on macrophages results in suppression of IL-12 production. We show that Fc gamma R ligation selectively down-regulates IL-12 p40 and p35 gene expression at the level of transcription. The region responsive to this inhibition maps to the Ets site of the p40 promoter. PU.1, IFN consensus sequence binding protein, and c-REL: form a complex on this element upon macrophage activation. Receptor ligation abolishes the binding of this PU.1-containing activation complex, and abrogates p40 transcription. A dominant-negative construct of PU.1 diminishes IL-12 p40 promoter activity and endogenous IL-12 p40 protein secretion. Thus, the specificity of IL-12 down-regulation following receptor ligation lies in the inhibition of binding of a PU.1-containing complex to the Ets site of the IL-12 promoter. These findings provide evidence demonstrating for the first time the importance of PU.1 in the transcriptional regulation of IL-12 gene expression.

DOI10.4049/jimmunol.166.7.4498
Alternate JournalJ Immunol
PubMed ID11254706
Grant ListAI-134412 / AI / NIAID NIH HHS / United States
AI-45899 / AI / NIAID NIH HHS / United States
AI-46805 / AI / NIAID NIH HHS / United States
CA-10815 / CA / NCI NIH HHS / United States
CA-32898 / CA / NCI NIH HHS / United States
CA-79772 / CA / NCI NIH HHS / United States

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