Central role for type I interferons and Tyk2 in lipopolysaccharide-induced endotoxin shock
(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)
Please use this url to cite or link to this publication:
https://lup.lub.lu.se/record/312464
- author
- organization
- publishing date
- 2003
- type
- Contribution to journal
- publication status
- published
- subject
- in
- Nature Immunology
- volume
- 4
- issue
- 5
- pages
- 471 - 477
- publisher
- Nature Publishing Group
- external identifiers
-
- wos:000182665400015
- pmid:12679810
- scopus:0038476601
- pmid:12679810
- ISSN
- 1529-2908
- DOI
- 10.1038/ni910
- language
- English
- LU publication?
- yes
- id
- 2446f80b-bd0b-42dc-9fae-b8b9cee61987 (old id 312464)
- date added to LUP
- 2016-04-01 16:25:29
- date last changed
- 2022-04-15 04:28:36
@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/10.1038/ni910}}, doi = {{10.1038/ni910}}, volume = {{4}}, year = {{2003}}, }