Publikation

Superoxide Dismutase 1 Protects Hepatocytes from Type I Interferon-Driven Oxidative Damage

Wissenschaftlicher Artikel/Review - 17.11.2015

Bereiche
PubMed
DOI

Zitation
Bhattacharya A, Arnold I, Flatz L, Xu H, Lang P, Aderem A, Takaoka A, Superti-Furga G, Colinge J, Ludewig B, Löhning M, Baazim H, Khamina K, Panse I, Hegazy A, Deigendesch N, Kosack L, Cupovic J, Kandasamy R, Hildebrandt A, Merkler D, Kühl A, Vilagos B, Schliehe C, Bergthaler A. Superoxide Dismutase 1 Protects Hepatocytes from Type I Interferon-Driven Oxidative Damage. Immunity 2015; 43:974-86.
Art
Wissenschaftlicher Artikel/Review (Englisch)
Zeitschrift
Immunity 2015; 43
Veröffentlichungsdatum
17.11.2015
eISSN (Online)
1097-4180
Seiten
974-86
Kurzbeschreibung/Zielsetzung

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.