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dc.contributor.authorChaisson, Michelle L.en_US
dc.contributor.authorBrooling, John T.en_US
dc.contributor.authorLadiges, Warrenen_US
dc.contributor.authorTsai, Sophiaen_US
dc.contributor.authorFausto, Nelsonen_US
dc.date.accessioned2010-04-21T15:56:15Z
dc.date.available2010-04-21T15:56:15Z
dc.date.issued2002-07-15en_US
dc.identifier.citationChaisson ML, Brooling JT, Ladiges W, Tsai S, Fausto N. Hepatocyte-specific inhibition of NF-κB leads to apoptosis after TNF treatment, but not after partial hepatectomy. J Clin Invest. 2002;110(2):193-202.en_US
dc.identifier.other10.1172/JCI15295en_US
dc.identifier.urihttp://www.jci.org/articles/view/15295en_US
dc.identifier.urihttp://hdl.handle.net/1773/15776
dc.description.abstractOne 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/ΔN-IκBα transgenic mice, in which expression of a deletion mutant of IκBα (ΔN-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 ΔN-IκBα, NF-κB nuclear translocation was blocked in 45% of hepatocytes, leading to apoptosis 4 hours after TNF injection. In contrast, expression of ΔN-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.en_US
dc.description.sponsorshipNIH grants CA-23226 and CA-74131 (N. Fausto). M.L. Chaisson was supported by NIHtraining grants CA-09437 and GM-07270.en_US
dc.language.isoen_USen_US
dc.titleHepatocyte-specific inhibition of NF-κB leads to apoptosis after TNF treatment, but not after partial hepatectomyen_US


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