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- Karaghiosoff, M, et al.
(författare)
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Central role for type I interferons and Tyk2 in lipopolysaccharide-induced endotoxin shock
- 2003
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Ingår i: Nature Immunology. - : Springer Science and Business Media LLC. - 1529-2908 .- 1529-2916. ; 4:5, s. 471-477
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Tidskriftsartikel (refereegranskat)abstract
- Toll-like receptor-4 activation by lipopolysaccharide (LPS) induces the expression of interferon-P (IFN-beta) in a MyD88-independent manner. Here we report that mice devoid of the JAK protein tyrosine kinase family member, Tyk2, were resistant to shock induced by high doses of LPS. Basal and LPS-induced expression of IFN-beta and IFN-alpha4 mRNA in Tyk2-null macrophages were diminished. However, Tyk2-null mice showed normal systemic production of nitric oxide and proinflammatory cytokines and the in vivo response to tumor necrosis factor (TNF) was unperturbed. IFN-beta-null but not STAT1-null mice were also resistant to high dose LPS treatment. Together, these data suggest that Tyk2 and IFN-beta are essential effectors in LPS induced lethality.
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