2026-08-29T10:38:19Zhttps://repisalud.isciii.es/rest/oai/requestoai:repisalud.isciii.es:20.500.12105/174172024-11-29T19:43:12Zcom_20.500.12105_2173com_20.500.12105_2051col_20.500.12105_19597
Repisalud
author
Thomsen, Martin K
author
Bakiri, Latifa
author
Hasenfuss, Sebastian C
author
Hamacher, Rainer
author
Martinez Garcia, Maria Dolores
author
Wagner, Erwin F
funder
Fundación BBVA
funder
Unión Europea. Comisión Europea. European Research Council (ERC)
funder
Instituto de Salud Carlos III
funder
European Molecular Biology Organization
funder
Gobierno de España
funder
German Research Foundation (DFG)
2024-02-01T15:09:59Z
2024-02-01T15:09:59Z
2013-12
J Clin Invest. 2013 123(12):5258-68.
10.1172/JCI70405
1558-8238
The Journal of clinical investigation
24200694
http://hdl.handle.net/20.500.12105/17417
Understanding the molecular pathogenesis of inflammatory liver disease is essential to design efficient therapeutic approaches. In hepatocytes, the dimeric transcription factor c-JUN/AP-1 is a major mediator of cell survival during hepatitis, although functions for other JUN proteins in liver disease are less defined. Here, we found that JUNB was specifically expressed in human and murine immune cells during acute liver injury. We analyzed the molecular function of JUNB in experimental models of hepatitis, including administration of concanavalin A (ConA) or α-galactosyl-ceramide, which induce liver inflammation and injury. Mice specifically lacking JUNB in hepatocytes displayed a mild increase in ConA-induced liver damage. However, targeted deletion of Junb in immune cells and hepatocytes protected against hepatitis in experimental models that involved NK/NKT cells. The absence of JUNB in immune cells decreased IFN-γ expression and secretion from NK and NKT cells, leading to reduced STAT1 pathway activation. Systemic IFN-γ treatment or adenovirus-based IRF1 delivery to Junb-deficient mice restored hepatotoxicity, and we demonstrate that Ifng is a direct transcriptional target of JUNB. These findings demonstrate that JUNB/AP-1 promotes cell death during acute hepatitis by regulating IFN-γ production in NK and NKT cells and thus functionally antagonizes the hepatoprotective function of c-JUN/AP-1 in hepatocytes.
eng
JUNB/AP-1 controls IFN-γ during inflammatory liver disease.
journal article
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application/pdf
JUNBAP-1controls-2013.pdf
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https://repisalud.isciii.es/bitstreams/4d7326f0-2ffd-434d-a377-537ebbe8870b/download
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text/plain
JUNBAP-1controls-2013.pdf.txt