Medizinische Universität Graz Austria/Österreich - Forschungsportal - Medical University of Graz
Gewählte Publikation:
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.
Central role for type I interferons and Tyk2 in lipopolysaccharide-induced endotoxin shock.
Nat Immunol. 2003; 4(5):471-477
Doi: 10.1038/ni910
Web of Science
PubMed
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- Co-Autor*innen der Med Uni Graz
- Kriegshäuser Gernot
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- 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.
- Find related publications in this database (using NLM MeSH Indexing)
- 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