Superoxide Dismutase 1 Protects Hepatocytes from Type I Interferon-Driven Oxidative Damage
| Autor: | Bhattacharya, Anannya, Hegazy, Ahmed N., Deigendesch, Nikolaus, Kosack, Lindsay, Cupovic, Jovana, Kandasamy, Richard K., Hildebrandt, Andrea, Merkler, Doron, Kühl, Anja A., Vilagos, Bojan, Schliehe, Christopher, Panse, Isabel, Khamina, Kseniya, Baazim, Hatoon, Arnold, Isabelle, Flatz, Lukas, Xu, Haifeng C., Lang, Philipp A., Aderem, Alan, Takaoka, Akinori, Superti-Furga, Giulio, Colinge, Jacques, Ludewig, Burkhard, Löhning, Max, Bergthaler, Andreas |
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| Přispěvatelé: | Charité - UniversitätsMedizin = Charité - University Hospital [Berlin], University of Oxford [Oxford], Deutsches Rheuma-ForschungsZentrum (DRFZ), Deutsches Rheuma-ForschungsZentrum, Max Planck Institute for Infection Biology (MPIIB), Max-Planck-Gesellschaft, Brustzentrum Kantonsspital St. Gallen, University of Geneva [Switzerland], Computer Science [Heinrich Heine University], Heinrich Heine Universität Düsseldorf = Heinrich Heine University [Düsseldorf], Hokkaido University [Sapporo, Japan], Medizinische Universität Wien = Medical University of Vienna, Institut de Recherche en Cancérologie de Montpellier (IRCM - U1194 Inserm - UM), CRLCC Val d'Aurelle - Paul Lamarque-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Montpellier (UM) |
| Jazyk: | angličtina |
| Rok vydání: | 2015 |
| Předmět: |
Transcription
Genetic T-Lymphocytes Immunology SOD1 ddc:616.07 medicine.disease_cause Antioxidants Article Superoxide dismutase Mice Superoxide Dismutase-1 Downregulation and upregulation Interferon medicine Animals Immunology and Allergy Inflammation Hepatitis biology Superoxide Dismutase medicine.disease Immunity Innate 3. Good health Killer Cells Natural Mice Inbred C57BL Oxidative Stress Hepatocytes Oxidative Damage Infectious Diseases Liver Hepatitis Viral Animal Interferon Type I biology.protein Cancer research Viral hepatitis Oxidation-Reduction [SDV.MHEP]Life Sciences [q-bio]/Human health and pathology Interferon type I Oxidative stress Signal Transduction medicine.drug |
| Zdroj: | Immunity, Vol. 43, No 5 (2015) pp. 974-986 Immunity Immunity, Elsevier, 2015, 43 (5), pp.974-986. ⟨10.1016/j.immuni.2015.10.013⟩ |
| ISSN: | 1074-7613 |
| DOI: | 10.1016/j.immuni.2015.10.013⟩ |
| Popis: | Summary Tissue damage caused by viral hepatitis is a major cause of morbidity and mortality worldwide. Using a mouse model of viral hepatitis, we identified virus-induced early transcriptional changes in the redox pathways in the liver, including downregulation of superoxide dismutase 1 (Sod1). Sod1−/− mice exhibited increased inflammation and aggravated liver damage upon viral infection, which was independent of T and NK cells and could be ameliorated by antioxidant treatment. Type I interferon (IFN-I) led to a downregulation of Sod1 and caused oxidative liver damage in Sod1−/− and wild-type mice. Genetic and pharmacological ablation of the IFN-I signaling pathway protected against virus-induced liver damage. These results delineate IFN-I mediated oxidative stress as a key mediator of virus-induced liver damage and describe a mechanism of innate-immunity-driven pathology, linking IFN-I signaling with antioxidant host defense and infection-associated tissue damage. Video Abstract Graphical Abstract Highlights • Viral infection leads to redox dysregulation including the downregulation of SOD1 • Sod1−/− mice exhibit aggravated viral hepatitis, which is rescued by antioxidants • IFN-I signaling via STAT1 drives SOD1 downregulation and early liver damage • Ablation of IFN-I signaling ameliorates viral hepatitis in Sod1−/− and WT mice Bergthaler and colleagues show that superoxide dismutase 1 protects the liver from type I interferon-driven oxidative damage in viral hepatitis. Liver damage was mediated by hepatocyte-intrinsic IFNAR1-STAT1 signaling. |
| Databáze: | OpenAIRE |
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