Type I interferon drives tumor necrosis factor-induced lethal shock.
Cast your vote
You can rate an item by clicking the amount of stars they wish to award to this item.
When enough users have cast their vote on this item, the average rating will also be shown.
Your vote was cast
Thank you for your feedback
Thank you for your feedback
Van Hauwermeiren, Filip
MetadataShow full item record
AbstractTumor necrosis factor (TNF) is reputed to have very powerful antitumor effects, but it is also a strong proinflammatory cytokine. Injection of TNF in humans and mice leads to a systemic inflammatory response syndrome with major effects on liver and bowels. TNF is also a central mediator in several inflammatory diseases. We report that type I interferons (IFNs) are essential mediators of the lethal response to TNF. Mice deficient in the IFN-alpha receptor 1 (IFNAR-1) or in IFN-beta are remarkably resistant to TNF-induced hypothermia and death. After TNF injection, IFNAR-1(-/-) mice produced less IL-6, had less bowel damage, and had less apoptosis of enterocytes and hepatocytes compared with wild-type (WT) mice. Extensive gene expression analysis in livers of WT and IFNAR-1(-/-) mice revealed a large deficiency in the response to TNF in the knockout mice, especially of IFN-stimulated response element-dependent genes, many of which encode chemokines. In livers of IFNAR-1(-/-) mice, fewer infiltrating white blood cells (WBCs) were detected by immunohistochemistry. Deficiency of type I IFN signaling provided sufficient protection for potentially safer therapeutic use of TNF in tumor-bearing mice. Our data illustrate that type I IFNs act as essential mediators in TNF-induced lethal inflammatory shock, possibly by enhancing cell death and inducing chemokines and WBC infiltration in tissues.
CitationType I interferon drives tumor necrosis factor-induced lethal shock. 2009, 206 (9):1873-82 J. Exp. Med.
AffiliationDepartment for Molecular Biomedical Research, VIB, Ghent B9052, Belgium.
The following license files are associated with this item:
- Organ-Specific Expression of IL-1 Receptor Results in Severe Liver Injury in Type I Interferon Receptor Deficient Mice.
- Authors: Anzaghe M, Resch T, Schaser E, Kronhart S, Diez C, Niles MA, Korotkova E, Schülke S, Wolfheimer S, Kreuz D, Wingerter M, Bartolomé Rodríguez MM, Waibler Z
- Issue date: 2019
- Interferon-beta expression and type I interferon receptor signaling of hepatocytes prevent hepatic necrosis and virus dissemination in Coxsackievirus B3-infected mice.
- Authors: Koestner W, Spanier J, Klause T, Tegtmeyer PK, Becker J, Herder V, Borst K, Todt D, Lienenklaus S, Gerhauser I, Detje CN, Geffers R, Langereis MA, Vondran FWR, Yuan Q, van Kuppeveld FJM, Ott M, Staeheli P, Steinmann E, Baumgärtner W, Wacker F, Kalinke U
- Issue date: 2018 Aug
- In Vivo Conditions Enable IFNAR-Independent Type I Interferon Production by Peritoneal CD11b+ Cells upon Thogoto Virus Infection.
- Authors: Kochs G, Anzaghe M, Kronhart S, Wagner V, Gogesch P, Scheu S, Lienenklaus S, Waibler Z
- Issue date: 2016 Oct 15
- Type I Interferon α/β Receptor-Mediated Signaling Negatively Regulates Antiviral Cytokine Responses in Murine Bone-Marrow-Derived Mast Cells and Protects the Cells from Virus-Induced Cell Death.
- Authors: Darzianiazizi M, Mehrani Y, Chan L, Mould RC, Kulkarni RR, Sharif S, Bridle BW, Karimi K
- Issue date: 2020 Nov 27
- Protection against RNA-induced liver damage by myeloid cells requires type I interferon and IL-1 receptor antagonist in mice.
- Authors: Conrad E, Resch TK, Gogesch P, Kalinke U, Bechmann I, Bogdan C, Waibler Z
- Issue date: 2014 Apr