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rdf:type |
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lifeskim:mentions |
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pubmed:issue |
2
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pubmed:dateCreated |
1999-7-29
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pubmed:abstractText |
Stimulation of the type 1 IL-1R (IL-1R1) and the IL-18R by their cognate ligands induces recruitment of the IL-1R-associated kinase (IRAK). Activation of IRAK leads in turn to nuclear translocation of NF-kappaB, which directs expression of innate and adaptive immune response genes. To study IRAK function in cytokine signaling, we generated cells and mice lacking the IRAK protein. IRAK-deficient fibroblasts show diminished activation of NF-kappaB when stimulated with IL-1. Immune effector cells without IRAK exhibit a defective IFN-gamma response to costimulation with IL-18. Furthermore, mice lacking the Irak gene demonstrate an attenuated response to injected IL-1. Deletion of Irak, however, does not affect the ability of mice to develop delayed-type hypersensitivity or clear infection with the intracellular parasite, Listeria monocytogenes. These results demonstrate that although IRAK participates in IL-1 and IL-18 signal transduction, residual cytokine responsiveness operates through an IRAK-independent pathway.
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pubmed:grant |
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pubmed:language |
eng
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pubmed:journal |
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pubmed:citationSubset |
AIM
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pubmed:chemical |
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pubmed:status |
MEDLINE
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pubmed:month |
Jul
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pubmed:issn |
0022-1767
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pubmed:author |
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pubmed:issnType |
Print
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pubmed:day |
15
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pubmed:volume |
163
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
978-84
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pubmed:dateRevised |
2010-11-18
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pubmed:meshHeading |
pubmed-meshheading:10395695-Animals,
pubmed-meshheading:10395695-Cell Line,
pubmed-meshheading:10395695-Cytokines,
pubmed-meshheading:10395695-Female,
pubmed-meshheading:10395695-Fertility,
pubmed-meshheading:10395695-Hypersensitivity, Delayed,
pubmed-meshheading:10395695-Immunologic Deficiency Syndromes,
pubmed-meshheading:10395695-Interleukin-1,
pubmed-meshheading:10395695-Interleukin-1 Receptor-Associated Kinases,
pubmed-meshheading:10395695-Interleukin-18,
pubmed-meshheading:10395695-Listeriosis,
pubmed-meshheading:10395695-Male,
pubmed-meshheading:10395695-Mice,
pubmed-meshheading:10395695-Mice, Inbred C57BL,
pubmed-meshheading:10395695-Mice, Knockout,
pubmed-meshheading:10395695-NF-kappa B,
pubmed-meshheading:10395695-Protein Kinases,
pubmed-meshheading:10395695-Receptors, Interleukin-1,
pubmed-meshheading:10395695-Sequence Deletion,
pubmed-meshheading:10395695-Signal Transduction,
pubmed-meshheading:10395695-Spleen,
pubmed-meshheading:10395695-Stem Cells,
pubmed-meshheading:10395695-Survival Analysis
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pubmed:year |
1999
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pubmed:articleTitle |
Impaired cytokine signaling in mice lacking the IL-1 receptor-associated kinase.
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pubmed:affiliation |
Department of Pediatrics, University of Texas Southwestern Medical Center, Dallas 75235, USA. jthomas@hamon.swmed.edu
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pubmed:publicationType |
Journal Article,
Research Support, U.S. Gov't, P.H.S.,
Research Support, Non-U.S. Gov't
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