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

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.

journal_name

Nat Immunol

journal_title

Nature immunology

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

doi

10.1038/ni910

keywords:

subject

Has Abstract

pub_date

2003-05-01 00:00:00

pages

471-7

issue

5

eissn

1529-2908

issn

1529-2916

pii

ni910

journal_volume

4

pub_type

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