Abstract
IL-10 has a well-characterized anti-inflammatory role that includes the suppression of inflammatory cytokine (e.g. TNF-alpha) production by monocytic/macrophage cells. Both transcriptional and post-transcriptional/translational mechanisms have been proposed to explain this process. In this study we observed that IL-10 inhibited nuclear NF kappa B DNA binding activity without affecting I kappa B degradation or translocation of NF kappa B subunits to the nucleus. While the suppression of NF kappa B in 70Z/3 pre-B cells correlated with suppression of NF kappa B transcriptional activity and expression of surface IgM, it did not correlate with the production of TNF-alpha mRNA or protein in RAW 264.7 macrophages. Similar observations in the macrophages were made with a second anti-inflammatory cytokine, IL-4. Therefore we conclude that although IL-10 or IL-4 can suppress NF kappa B activity, this appears to have little effect on the expression of the TNF-alpha gene and is unlikely to be the basis of the anti-inflammatory effects of these cytokines.
MeSH terms
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Animals
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Biological Transport
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Cell Line
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Cell Nucleus / metabolism
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DNA / immunology
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DNA / metabolism
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DNA-Binding Proteins / metabolism
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I-kappa B Proteins*
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Immunosuppressive Agents / pharmacology*
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Interleukin-10 / physiology*
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Interleukin-4 / physiology
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Lipopolysaccharides / antagonists & inhibitors
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Lipopolysaccharides / pharmacology
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Macrophages / metabolism
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Mice
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NF-KappaB Inhibitor alpha
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NF-kappa B / antagonists & inhibitors*
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NF-kappa B / metabolism*
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NF-kappa B p50 Subunit
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Protein Binding / immunology
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RNA, Messenger / drug effects
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RNA, Messenger / metabolism
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Transcription Factor RelA
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Transcription, Genetic / drug effects
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Transcription, Genetic / immunology
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Tumor Necrosis Factor-alpha / antagonists & inhibitors*
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Tumor Necrosis Factor-alpha / biosynthesis*
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Tumor Necrosis Factor-alpha / genetics
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Tumor Necrosis Factor-alpha / metabolism
Substances
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DNA-Binding Proteins
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I kappa B beta protein
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I-kappa B Proteins
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Immunosuppressive Agents
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Lipopolysaccharides
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NF-kappa B
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NF-kappa B p50 Subunit
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Nfkbia protein, mouse
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RNA, Messenger
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Transcription Factor RelA
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Tumor Necrosis Factor-alpha
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Interleukin-10
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NF-KappaB Inhibitor alpha
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Interleukin-4
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DNA