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Selected Publication:

Type of publication: Journal Article
Type of document: Full Paper

Year: 2003

Authors: Karaghiosoff, M; Steinborn, R; Kovarik, P; Kriegshäuser, G; Baccarini, M; Donabauer, B; Reichart, U; Kolbe, T; Bogdan, C; Leanderson, T; Levy, D; Decker, T; Müller, M

Title: Central role for type I interferons and Tyk2 in lipopolysaccharide-induced endotoxin shock.

Source: Nat Immunol. 2003; 4(5):471-477



Authors Vetmeduni Vienna:

Karaghiosoff Marina
Kolbe Thomas
Müller Mathias
Reichart Ursula
Steinborn Ralf

Vetmed Research Units
Institut für In-vivo und In-vitro-Modelle
Institute of Animal Breeding and Genetics


Abstract:
Toll-like receptor-4 activation by lipopolysaccharide (LPS) induces the expression of interferon-beta (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.

Keywords Pubmed: Animals
Cytokines/biosynthesis
DNA-Binding Proteins/deficiency
DNA-Binding Proteins/genetics
DNA-Binding Proteins/metabolism
Female
Gene Expression
Interferon Regulatory Factor-1
Interferon Regulatory Factor-7
Interferon Type I/genetics*
Interferon-alpha/genetics
Interferon-beta/genetics
Lipopolysaccharides/toxicity
Macrophage Activation
Male
Mice
Mice, Inbred C57BL
Mice, Knockout
Nitric Oxide/biosynthesis
Phosphoproteins/genetics
Protein-Tyrosine Kinases/deficiency
Protein-Tyrosine Kinases/genetics
Protein-Tyrosine Kinases/metabolism*
Proteins/genetics
Proteins/metabolism*
RNA, Messenger/genetics
RNA, Messenger/metabolism
STAT1 Transcription Factor
Shock, Septic/etiology
Shock, Septic/genetics
Shock, Septic/immunology*
TYK2 Kinase
Trans-Activators/deficiency
Trans-Activators/genetics
Trans-Activators/metabolism


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