Linked Life Data

17431229

Source:http://linkedlifedata.com/resource/pubmed/id/17431229

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
4
pubmed:dateCreated
2007-6-8
pubmed:abstractText
The proinflammatory cytokine TNF has a pivotal role in liver pathophysiology because it holds the capacity to induce both hepatocyte cell death and hepatocyte proliferation. This dual effect of TNF on hepatocytes reflects its ability to induce both nuclear factor kappaB (NF-kappaB)-dependent gene expression and cell death. Multiple studies have demonstrated the crucial role of the transcription factor NF-kappaB in the decision between life and death of a hepatocyte. Massive hepatocyte apoptosis preceding embryonic lethality in NF-kappaB-deficient mice constituted the first indication of an essential antiapoptotic function of NF-kappaB in the liver. Although many studies confirmed this crucial cytoprotective role of NF-kappaB in adult liver, a number of genetic studies recently obtained conflicting results on the exact role of NF-kappaB in different mouse models of TNF hepatotoxicity, demonstrating that caution should be taken when interpreting studies using different NF-kappaB-deficient mice in distinct models of liver injury. Recent reports showing a role for hepatic NF-kappaB activation in the proliferation of malignant cells during hepatocarcinogenesis, and in the progression of fatty liver diseases to insulin resistance and type 2 diabetes mellitus demonstrate that NF-kappaB can also have more detrimental effects in the liver. Moreover, its role in the development of the metabolic syndrome emphasizes that hepatic NF-kappaB activation might also have adverse effects on the endocrine system. Therefore, understanding the regulation of hepatic TNF signaling and NF-kappaB activation is of critical therapeutic importance. In this review, we summarize how studies on the role of NF-kappaB in different mouse models of liver pathologies have contributed to this understanding.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Jun
pubmed:issn
0163-769X
pubmed:author
pubmed:issnType
Print
pubmed:volume
28
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
365-86
pubmed:meshHeading
pubmed:year
2007
pubmed:articleTitle
Hepatic tumor necrosis factor signaling and nuclear factor-kappaB: effects on liver homeostasis and beyond.
pubmed:affiliation
Department for Molecular Biomedical Research, VIB, Ghent University, Technologiepark 927, B-9052 Ghent (Zwijnaarde), Belgium.
pubmed:publicationType
Journal Article, Review, Research Support, Non-U.S. Gov't