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

Karaghiosoff, M; Steinborn, R; Kovarik, P; Kriegshauser, G; Baccarini, M; Donabauer, B; Reichart, U; Kolbe, T; Bogdan, C and Leanderson, Tomas LU , et al. (2003) In Nature Immunology 4(5). p.471-477
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... (More)
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. (Less)
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Nature Immunology
volume
4
issue
5
pages
471 - 477
publisher
Nature Publishing Group
external identifiers
  • wos:000182665400015
  • pmid:12679810
  • scopus:0038476601
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1529-2908
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English
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yes
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2446f80b-bd0b-42dc-9fae-b8b9cee61987 (old id 312464)
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2007-09-13 15:33:27
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2018-06-24 04:38:42
@article{2446f80b-bd0b-42dc-9fae-b8b9cee61987,
  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.},
  author       = {Karaghiosoff, M and Steinborn, R and Kovarik, P and Kriegshauser, G and Baccarini, M and Donabauer, B and Reichart, U and Kolbe, T and Bogdan, C and Leanderson, Tomas and Levy, D and Decker, T and Muller, M},
  issn         = {1529-2908},
  language     = {eng},
  number       = {5},
  pages        = {471--477},
  publisher    = {Nature Publishing Group},
  series       = {Nature Immunology},
  title        = {Central role for type I interferons and Tyk2 in lipopolysaccharide-induced endotoxin shock},
  url          = {http://dx.doi.org/},
  volume       = {4},
  year         = {2003},
}