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STING-IRF3 pathway links endoplasmic reticulum stress with hepatocyte apoptosis in early alcoholic liver disease

2013; National Academy of Sciences; Volume: 110; Issue: 41 Linguagem: Inglês

10.1073/pnas.1308331110

1091-6490

Jan Petrášek, Arvin Iracheta‐Vellve, Tímea Csák, Abhishek Satishchandran, Karen Kodys, Evelyn A. Kurt‐Jones, Katherine A. Fitzgerald, Gyöngyi Szabó,

Endoplasmic Reticulum Stress and Disease

Significance This paper provides previously undescribed evidence that STING, an endoplasmic reticulum (ER)-resident protein involved in DNA sensing, couples ER stress with apoptotic signaling in alcoholic liver disease. The proapoptotic role of STING is mediated by the interferon regulatory factor 3 (IRF3), and this is independent of inflammation or Type-I interferons. Activation of STING and IRF3, originally reported in the context of antiviral response, determines survival of hepatocytes in early alcoholic liver disease suggesting that innate immunity regulates hepatocyte pathophysiology independent of inflammation.