Abstract
Lipopolysaccharide (LPS) induction of the gene encoding interleukin 12 p40 requires remodeling of a promoter-encompassing nucleosome and the Toll-like receptor (TLR)-mediated activation of a c-Rel-containing complex. Analysis of TLR4-mutant mice revealed that remodeling requires TLR signaling. However, Rel proteins and other proteins required for transcription of an integrated p40 promoter were insufficient for remodeling. c-Rel was also unnecessary for remodeling, as remodeling was observed in c-Rel-/- macrophages, which lack p40 transcripts. These results suggest that remodeling requires TLR signaling pathways that diverge from the c-Rel activation pathways. The factors that stimulate remodeling may represent, therefore, newly identified targets of TLR signaling and of agents that regulate inflammatory responses and TH1 development.
Publication types
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Research Support, Non-U.S. Gov't
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Research Support, U.S. Gov't, P.H.S.
MeSH terms
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Animals
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CCAAT-Enhancer-Binding Proteins / metabolism
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Cell Line
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DNA Restriction Enzymes / metabolism
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Drosophila Proteins*
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Inflammation / etiology
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Inflammation / immunology
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Inflammation / metabolism
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Interleukin-12 / genetics*
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Lipopolysaccharides / toxicity
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Macrophages / immunology
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Macrophages / metabolism
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Membrane Glycoproteins / metabolism*
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Mice
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Mice, Inbred C3H
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Mice, Inbred C57BL
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Mice, Knockout
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Mice, Mutant Strains
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Nuclear Proteins / metabolism
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Nucleosomes / metabolism*
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Promoter Regions, Genetic*
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Proto-Oncogene Proteins c-rel / metabolism
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Receptors, Cell Surface / metabolism*
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Signal Transduction
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Th1 Cells / immunology
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Th1 Cells / metabolism
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Toll-Like Receptor 4
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Toll-Like Receptors
Substances
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CCAAT-Enhancer-Binding Proteins
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Drosophila Proteins
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Lipopolysaccharides
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Membrane Glycoproteins
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Nuclear Proteins
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Nucleosomes
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Proto-Oncogene Proteins c-rel
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Receptors, Cell Surface
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Toll-Like Receptor 4
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Toll-Like Receptors
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Interleukin-12
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DNA Restriction Enzymes