Dusp16 in Innate Immune Cells Immunology

MAPK activity is negatively regulated by members of the dual specificity phosphatase (Dusp) family, which differ in expression, substrate specificity, and subcellular localization. Here, we investigated the function of Dusp16/MKP-7 in the innate immune system. The Dusp16 isoforms A1 and B1 were inducibly expressed in macrophages and dendritic cells following Toll-like receptor stimulation. A gene trap approach was used to generate Dusp16-deficient mice. Homozygous Dusp16tp/tp mice developed without gross abnormalities but died perinatally. Fetal liver cells from Dusp16tp/tp embryos efficiently reconstituted the lymphoid and myeloid compartments with Dusp16-deficient hematopoietic cells. However, GM-CSF-induced proliferation of bone marrow progenitors in vitro was impaired in the absence of Dusp16. In vivo challenge with Escherichia coli LPS triggered higher production of IL-12p40 in mice with a Dusp16-deficient immune system. In vitro, Dusp16-deficient macrophages, but not dendritic cells, selectively overexpressed a subset of TLR-induced genes, including the cytokine IL-12. Dusp16-deficient fibroblasts showed enhanced activation of p38 and JNK MAPKs. In macrophages, pharmacological inhibition and siRNA knockdown of JNK1/2 normalized IL-12p40 secretion. Production of IL-10 and its inhibitory effect on IL-12 production were unaltered in Dusp16tp/tp macrophages. Altogether, the Dusp16 gene trap mouse model identifies an essential role in perinatal survival and reveals selective...
Source: Journal of Biological Chemistry - Category: Chemistry Authors: Tags: Signal Transduction Source Type: research

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Source: Expert Review of Gastroenterology and Hepatology - Category: Gastroenterology Tags: Expert Rev Gastroenterol Hepatol Source Type: research
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Source: European Journal of Pediatrics - Category: Pediatrics Source Type: research
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Source: International Journal of Microbiology - Category: Microbiology Tags: Int J Microbiol Source Type: research
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Source: Journal of the Brazilian Chemical Society - Category: Chemistry Source Type: research
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Source: Journal of Hazardous Materials - Category: Environmental Health Source Type: research
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Source: Biomedica : Revista del Instituto Nacional de Salud - Category: International Medicine & Public Health Tags: Biomedica Source Type: research
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Source: BMC Infectious Diseases - Category: Infectious Diseases Authors: Tags: Research article Source Type: research
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