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

被引：58

作者：

Bhattacharya, Anannya ^{[1
]}

Hegazy, Ahmed N. ^{[2
,3
,4
]}

Deigendesch, Nikolaus ^{[5
]}

Kosack, Lindsay ^{[1
]}

Cupovic, Jovana ^{[6
]}

Kandasamy, Richard K. ^{[1
]}

Hildebrandt, Andrea ^{[1
]}

Merkler, Doron ^{[7
,8
]}

Kuehl, Anja A. ^{[9
]}

Vilagos, Bojan ^{[1
]}

Schliehe, Christopher ^{[1
]}

Panse, Isabel ^{[2
,3
]}

Khamina, Kseniya ^{[1
]}

Baazim, Hatoon ^{[1
]}

Arnold, Isabelle ^{[4
]}

Flatz, Lukas ^{[6
]}

Xu, Haifeng C. ^{[10
]}

Lang, Philipp A. ^{[10
,11
]}

Aderem, Alan ^{[12
]}

Takaoka, Akinori ^{[13
]}

Superti-Furga, Giulio ^{[1
,14
]}

Colinge, Jacques ^{[1
]}

Ludewig, Burkhard ^{[6
]}

Loehning, Max ^{[2
,3
]}

Bergthaler, Andreas ^{[1
]}

机构：

[1] Austrian Acad Sci, CeMM Res Ctr Mol Med, A-1090 Vienna, Austria

[2] Charite, Dept Rheumatol & Clin Immunol, Expt Immunol, D-10117 Berlin, Germany

[3] Leibniz Inst, German Rheumatism Res Ctr DRFZ, D-10117 Berlin, Germany

[4] Univ Oxford, John Radcliffe Hosp, Nuffield Dept Clin Med, Div Expt Med,Translat Gastroenterol Unit, Oxford OX3 9DU, England

[5] Max Planck Inst Infect Biol, D-10117 Berlin, Germany

[6] Cantonal Hosp St Gallen, Inst Immunobiol, CH-9007 St Gallen, Switzerland

[7] Univ Geneva, Dept Pathol & Immunol, Ctr Med Univ, CH-1211 Geneva, Switzerland

[8] Univ Med Gottingen, Dept Neuropathol, D-37099 Gottingen, Germany

[9] Charite, Dept Med Gastroenterol Infect Dis & Rheumatol 1, D-12200 Berlin, Germany

[10] Univ Dusseldorf, Dept Gastroenterol, D-40225 Dusseldorf, Germany

[11] Univ Dusseldorf, Dept Mol Med 2, D-40225 Dusseldorf, Germany

[12] Seattle Biomed Res Inst, Seattle, WA 98109 USA

[13] Hokkaido Univ, Inst Med Genet, Div Signaling Canc & Immunol, Sapporo, Hokkaido 0600815, Japan

[14] Med Univ Vienna, Ctr Physiol & Pharmacol, A-1090 Vienna, Austria

来源：

IMMUNITY | 2015年 / 43卷 / 05期

基金：

瑞士国家科学基金会;

关键词：

T-CELLS; VIRAL-INFECTION; VIRUS-INFECTION; FUNCTIONAL-ROLE; LIVER FIBROSIS; STRESS; ALPHA; DISEASE; PATHOGENESIS; MACROPHAGES;

D O I：

10.1016/j.immuni.2015.10.013

中图分类号：

R392 [医学免疫学]; Q939.91 [免疫学];

学科分类号：

071005 [微生物学]; 100108 [医学免疫学];

摘要：

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.

引用

页码：974 / 986

页数：13

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