Type I interferon drives tumor necrosis factor-induced lethal shock.
dc.contributor.author | Huys, Liesbeth | |
dc.contributor.author | Van Hauwermeiren, Filip | |
dc.contributor.author | Dejager, Lien | |
dc.contributor.author | Dejonckheere, Eline | |
dc.contributor.author | Lienenklaus, Stefan | |
dc.contributor.author | Weiss, Siegfried | |
dc.contributor.author | Leclercq, Georges | |
dc.contributor.author | Libert, Claude | |
dc.date.accessioned | 2009-12-02T15:31:30Z | |
dc.date.available | 2009-12-02T15:31:30Z | |
dc.date.issued | 2009-08-31 | |
dc.identifier.citation | Type I interferon drives tumor necrosis factor-induced lethal shock. 2009, 206 (9):1873-82 J. Exp. Med. | en |
dc.identifier.issn | 1540-9538 | |
dc.identifier.pmid | 19687227 | |
dc.identifier.doi | 10.1084/jem.20090213 | |
dc.identifier.uri | http://hdl.handle.net/10033/87237 | |
dc.description.abstract | Tumor 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. | |
dc.language.iso | en | en |
dc.subject.mesh | Animals | en |
dc.subject.mesh | Gene Expression Profiling | en |
dc.subject.mesh | Hypothermia | en |
dc.subject.mesh | Immunohistochemistry | en |
dc.subject.mesh | In Situ Nick-End Labeling | en |
dc.subject.mesh | Interferon Type I | en |
dc.subject.mesh | Interleukin-6 | en |
dc.subject.mesh | Liver | en |
dc.subject.mesh | Mice | en |
dc.subject.mesh | Mice, Knockout | en |
dc.subject.mesh | Receptor, Interferon alpha-beta | en |
dc.subject.mesh | Signal Transduction | en |
dc.subject.mesh | Systemic Inflammatory Response Syndrome | en |
dc.subject.mesh | Tumor Necrosis Factor-alpha | en |
dc.title | Type I interferon drives tumor necrosis factor-induced lethal shock. | en |
dc.type | Article | en |
dc.contributor.department | Department for Molecular Biomedical Research, VIB, Ghent B9052, Belgium. | en |
dc.identifier.journal | The Journal of experimental medicine | en |
refterms.dateFOA | 2018-06-12T22:08:14Z | |
html.description.abstract | Tumor 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. |