Abstract
We have generated mice with a cell type-specific disruption of the Stat3 gene in macrophages and neutrophils. The mutant mice are highly susceptible to endotoxin shock with increased production of inflammatory cytokines such as TNF alpha, IL-1, IFN gamma, and IL-6. Endotoxin-induced production of inflammatory cytokines is augmented because the suppressive effects of IL-10 on inflammatory cytokine production from macrophages and neutrophils are completely abolished. The mice show a polarized immune response toward the Th1 type and develop chronic enterocolitis with age. Taken together, Stat3 plays a critical role in deactivation of macrophages and neutrophils mainly exerted by IL-10.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Animals
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Cell Differentiation / immunology
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Chronic Disease
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Crosses, Genetic
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DNA-Binding Proteins / genetics*
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Enterocolitis / genetics*
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Enterocolitis / immunology*
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Enterocolitis / pathology
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Genetic Predisposition to Disease
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Interleukin-10 / physiology
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Lipopolysaccharides / toxicity
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Macrophage Activation / genetics
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Macrophages, Peritoneal / metabolism*
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Mice
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Mice, Inbred C57BL
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Mice, Inbred Strains
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Mice, Knockout
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Neutrophils / metabolism*
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STAT3 Transcription Factor
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Shock, Septic / genetics
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Shock, Septic / immunology
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Th1 Cells / immunology*
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Th1 Cells / pathology
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Trans-Activators / genetics*
Substances
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DNA-Binding Proteins
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Lipopolysaccharides
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STAT3 Transcription Factor
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Stat3 protein, mouse
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Trans-Activators
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Interleukin-10