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

Summary, in English

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.

• Författare: M Karaghiosoff; R Steinborn; P Kovarik; G Kriegshauser; M Baccarini; B Donabauer; U Reichart; T Kolbe; C Bogdan; Tomas Leanderson; D Levy; T Decker; M Muller
• Avdelning/ar: Immunology
• Publiceringsår: 2003
• Språk: Engelska
• Sidor: 471-477
• Publikation/Tidskrift/Serie: Nature Immunology
• Volym: 4
• Issue: 5
• Länkar: http://dx.doi.org/10.1038/ni910
• Dokumenttyp: Artikel i tidskrift
• Förlag: Nature Publishing Group
• Ämne: Immunology in the medical area
• Status: Published
• Forskningsgrupp: Immunology
• ISBN/ISSN/Övrigt: ISSN: 1529-2908