Linked Life Data

10692445

Source:http://linkedlifedata.com/resource/pubmed/id/10692445

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
9
pubmed:dateCreated
2000-4-3
pubmed:abstractText
NFkappaB is an essential survival factor in several physiological conditions such as embryonal liver development and liver regeneration. However, NFkappaB is also a main mediator of the cellular response to a variety of extracellular stress stimuli, and it has been shown that some viral-induced host cell apoptosis appears to be dependent on NFkappaB activation. The activation of NFkappaB upon viral infection may be a rapid way of initiating an innate immune response against the viral particles. We have assessed the role of NFkB during the early phase of adenoviral hepatitis in a nude mouse model using an adenoviral vector expressing a mutant form of IkappaBalpha. Administration of a LacZ-expressing adenoviral vector induces NFkB DNA and correlates with the up-regulation of Fas (CD95) mRNA, but not FasL (CD95L) mRNA, during the early phase of adenoviral hepatitis. The rapid increase in NFkappaB DNA binding after adenoviral infection of the liver could be very effectively inhibited by IkappaBalpha. Compared with the LacZ control virus, the IkappaBalpha-expressing adenoviral vector inhibits the increase of Fas (CD95) mRNA expression, in particular in the very early phase of the hepatitis. Reporter gene experiments in hepatoma cell lines with a Fas promoter-luciferase construct indicated that the repression of Fas (CD95) mRNA by IkappaBalpha was transcriptionally mediated. The functional relevance of the NFkappaB-dependent increase in Fas (CD95) transcription was assessed by caspase 3 assays and terminal dUTP nick-end labeling tests. Compared with the control, IkappaBalpha adenoviral infection resulted in reduced caspase 3 activity during the early phase of viral hepatitis and in a prevention of liver cell apoptosis 24 h after adenoviral administration. Therefore our study demonstrates a new pro-apoptotic function of NFkappaB in Fas (CD95)-mediated apoptosis of hepatocytes. Interestingly, NFkappaB mediates liver cell apoptosis upon viral infection even in a phase where tumor necrosis factor-alpha is already induced, as shown by the time curves of tumor necrosis factor-alpha serum levels. Therefore, the pro- or anti-apoptotic role of NFkappaB appears to be more determined by the nature of the death stimulus than by the origin of the tissue.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Mar
pubmed:issn
0021-9258
pubmed:author
pubmed:issnType
Print
pubmed:day
3
pubmed:volume
275
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
6421-7
pubmed:dateRevised
2008-11-21
pubmed:meshHeading
pubmed-meshheading:10692445-Adenoviridae Infections, pubmed-meshheading:10692445-Animals, pubmed-meshheading:10692445-Antigens, CD95, pubmed-meshheading:10692445-Apoptosis, pubmed-meshheading:10692445-Caspase 3, pubmed-meshheading:10692445-Caspases, pubmed-meshheading:10692445-Cell Line, pubmed-meshheading:10692445-DNA-Binding Proteins, pubmed-meshheading:10692445-Genes, Reporter, pubmed-meshheading:10692445-Hepatitis, Animal, pubmed-meshheading:10692445-Humans, pubmed-meshheading:10692445-I-kappa B Proteins, pubmed-meshheading:10692445-In Situ Nick-End Labeling, pubmed-meshheading:10692445-Liver, pubmed-meshheading:10692445-Mice, pubmed-meshheading:10692445-Mice, Nude, pubmed-meshheading:10692445-NF-kappa B, pubmed-meshheading:10692445-RNA, Messenger, pubmed-meshheading:10692445-Transcriptional Activation, pubmed-meshheading:10692445-Tumor Necrosis Factor-alpha
pubmed:year
2000
pubmed:articleTitle
NFkappaB mediates apoptosis through transcriptional activation of Fas (CD95) in adenoviral hepatitis.
pubmed:affiliation
Department of Gastroenterology and Hepatology, Medizinische Hochschule, 30625 Hannover, Germany.
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't