Potential conflict of interest: Nothing to report.
Activation and function of hepatocyte NF-κB in postischemic liver injury†
Article first published online: 16 JUN 2005
Copyright © 2005 American Association for the Study of Liver Diseases
Volume 42, Issue 1, pages 216–218, July 2005
How to Cite
Lentsch, A. B. (2005), Activation and function of hepatocyte NF-κB in postischemic liver injury. Hepatology, 42: 216–218. doi: 10.1002/hep.20779
- Issue published online: 16 JUN 2005
- Article first published online: 16 JUN 2005
The inhibitor of NF-κB (I-κB) kinase (IKK) complex consists of 3 subunits, IKK1, IKK2, and NF-κB essential modulator (NEMO), and is involved in the activation of NF-κB by various stimuli. IKK2 or NEMO constitutive knockout mice die during embryogenesis as a result of massive hepatic apoptosis. Therefore, we examined the role of IKK2 in TNF-induced apoptosis and ischemia/reperfusion (I/R) injury in the liver by using conditional knockout mice. Hepatocyte-specific ablation of IKK2 did not lead to impaired activation of NF-κB or increased apoptosis after TNF-alpha stimulation whereas conditional NEMO knockout resulted in complete block of NF-κB activation and massive hepatocyte apoptosis. In a model of partial hepatic I/R injury, mice lacking IKK2 in hepatocytes displayed significantly reduced liver necrosis and inflammation than wild-type mice. AS602868, a novel chemical inhibitor of IKK2, protected mice from liver injury due to I/R without sensitizing them toward TNF-induced apoptosis and could therefore emerge as a new pharmacological therapy for liver resection, hemorrhagic shock, or transplantation surgery.