Abstract
IL-4 promotes allergic responses and inhibits the production of proinflammatory cytokines by monocytes and macrophages. The promotion of allergic responses by IL-4 has been shown to be absolutely dependent on the transcription factor STAT6. We report here that the inhibitory effects of IL-4 on the production of TNF-alpha or IL-12 by macrophages had both STAT6-dependent and -independent components, depending on the stimuli. IL-4 failed to inhibit the release of TNF-alpha or IL-12 from STAT6 null macrophages stimulated with LPS alone. However, IL-4 still induced significant inhibition of the production of TNF-alpha and IL-12 from STAT6 null macrophages that were stimulated with the more physiologically relevant combination of LPS and IFN-gamma. These data show that STAT6 is required for the IL-4-mediated inhibition of the production of TNF-alpha and IL-12 stimulated by LPS alone, but that IL-4 also activates distinct, STAT6 independent mechanism(s) that inhibit the IFN-gamma-mediated enhancement of IL-12 and TNF-alpha production.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Adjuvants, Immunologic / physiology
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Animals
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DNA-Binding Proteins / metabolism
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Interferon-gamma / physiology
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Interleukin-12 / antagonists & inhibitors*
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Interleukin-12 / biosynthesis*
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Interleukin-4 / physiology*
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Lipopolysaccharides / pharmacology
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Macrophage Activation / immunology
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Macrophages, Peritoneal / immunology
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Macrophages, Peritoneal / metabolism
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Mice
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Mice, Inbred BALB C
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Mice, Mutant Strains
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Phosphorylation
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STAT1 Transcription Factor
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STAT6 Transcription Factor
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Signal Transduction / immunology
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Trans-Activators / deficiency
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Trans-Activators / genetics
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Trans-Activators / metabolism
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Trans-Activators / physiology*
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Tumor Necrosis Factor-alpha / antagonists & inhibitors*
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Tumor Necrosis Factor-alpha / biosynthesis*
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Tyrosine / metabolism
Substances
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Adjuvants, Immunologic
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DNA-Binding Proteins
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Lipopolysaccharides
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STAT1 Transcription Factor
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STAT6 Transcription Factor
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Stat1 protein, mouse
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Stat6 protein, mouse
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Trans-Activators
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Tumor Necrosis Factor-alpha
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Interleukin-12
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Interleukin-4
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Tyrosine
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Interferon-gamma