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

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

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dc.contributor.author Chaisson, Michelle L. en_US
dc.contributor.author Brooling, John T. en_US
dc.contributor.author Ladiges, Warren en_US
dc.contributor.author Tsai, Sophia en_US
dc.contributor.author Fausto, Nelson en_US
dc.date.accessioned 2010-04-21T15:56:15Z
dc.date.available 2010-04-21T15:56:15Z
dc.date.issued 2002-07-15 en_US
dc.identifier.citation Chaisson 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.other 10.1172/JCI15295 en_US
dc.identifier.uri http://www.jci.org/articles/view/15295 en_US
dc.identifier.uri http://hdl.handle.net/1773/15776
dc.description.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/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.sponsorship NIH 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.iso en_US en_US
dc.title Hepatocyte-specific inhibition of NF-κB leads to apoptosis after TNF treatment, but not after partial hepatectomy en_US


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