Work

Hepatocyte-specific inhibition of NF-κB leads to apoptosis after TNF treatment, but not after partial hepatectomy

Year: 2002

Type: article

Abstract: One of the earliest TNF-dependent events to occur during liver regeneration is the activation of the transcription factor NF-κB through TNF receptor type 1. NF-κB activation in the liver can have both antiapoptotic and proliferative effects, but it is unclear which liver cell types, hepatocytes or nonparenchymal cells (NPCs), contribute to these effects.To specifically evaluate the role of hepatocyte NF-κB, we created GLVP/∆N-IκBα transgenic mice, in which expression of a deletion mutant of IκBα (∆N-IκBα) was induced in hepatocytes after injection of mifepristone.In control mice, injection of 25 µg/kg TNF caused NF-κB nuclear translocation in virtually all hepatocytes by 30 minutes and no detectable apoptosis, while in mice expressing ∆N-IκBα, NF-κB nuclear translocation was blocked in 45% of hepatocytes, leading to apoptosis 4 hours after TNF injection.In contrast, expression of ∆N-IκBα in hepatocytes during the first several hours after partial hepatectomy did not lead to apoptosis or decreased proliferation.As NF-κB activation was not inhibited in liver NPCs, it is likely that these cells are responsible for mediating the proliferative and antiapoptotic effects of NF-κB during liver regeneration.

Source: Journal of Clinical Investigation

DOI: 10.1172/jci200215295

Authors: Michelle L. Chaisson, John T. Brooling, Warren Ladiges, Sophia Tsai, Nelson Fausto

Institutions: University of Washington, Baylor College of Medicine

Language: English

Topic: Liver physiology and pathology

Subfield: Hepatology

Field: Medicine

Domain: Health Sciences

SDG: Good health and well-being

Open Access status: bronze

Funder: National Institutes of Health