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Am J Physiol Gastrointest Liver Physiol. 2003 Oct;285(4):G761-8. Epub 2003 Jun 19.

STAT1 plays an essential role in LPS/D-galactosamine-induced liver apoptosis and injury.

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1
Section on Liver Biology, National Institute on Alcohol Abuse and Alcoholism/National Institutes of Health, Bethesda, MD 20892, USA.

Abstract

Interferon-gamma (IFN-gamma) has been implicated in liver damage in animal models and chronic hepatitis C infection; however, the underlying mechanism is not clear. Here we examined the role of STAT1, a key signaling molecule for IFN-gamma, in a model of murine hepatitis induced by the injection of LPS/D-galactosamine and in human hepatoma Hep3B cells. STAT1 is rapidly activated and highly induced after injection of LPS/D-galactosamine. Both overexpression of STAT1 and hepatocellular damage are located in the same pericentral region. Disruption of the STAT1 gene abolishes LPS/D-galactosamine-induced liver injury. Studies from IFN-gamma-deficient mice indicate that IFN-gamma is the major cytokine responsible for activation and hyperexpression of STAT1 in LPS/D-galactosamine-induced hepatitis. Hep3B cells overexpressing dominant negative STAT1 are resistant to IFN-gamma and IFN-gamma + TNF-alpha-induced cell death, whereas Hep3B cells overexpressing wild-type STAT1 are more susceptible to cell death. Taken together, these findings suggest that STAT1 plays an essential role in LPS/D-galactosamine-induced liver apoptosis and injury.

PMID:
12816762
DOI:
10.1152/ajpgi.00224.2003
[Indexed for MEDLINE]
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