Source:http://linkedlifedata.com/resource/pubmed/id/11753206
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| Predicate | Object |
|---|---|
| rdf:type | |
| lifeskim:mentions | |
| pubmed:issue |
5
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| pubmed:dateCreated |
2001-12-25
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| pubmed:abstractText |
Lipopolysaccharide and D-galactosamine induced lethality and apoptotic liver injury is dependent upon endogenously produced TNF-alpha. Unlike the response to high dose lipopolysaccharide alone, death in this model is a direct result of hepatocyte apoptosis. In a series of recent studies, we have demonstrated that mortality and hepatic injury following lipopolysaccharide administration in D-galactosamine-sensitized mice is dependent upon secreted 17 kDa TNF-alpha acting primarily through the p55 TNF receptor. Transgenic mice expressing null forms of TNF-alpha, the p55 receptor, or expressing only a cell-associated form of TNF-alpha exhibited no mortality and only modest liver injury when challenged with 8 mg of D-galactosamine and 100 ng of lipopolysaccharide. Although Fas ligand expression is increased in the liver, it appeared to play no significant role in outcome, since mice expressing a mutant form of Fas ligand are still sensitive to LPS- and D-galactosamine-induced lethality. Finally, we have seen significant variation in LPS- and D-galactosamine-mediated lethality among different strains of mice. The non-obese diabetic or NOD mouse is highly resistant to LPS-and D-galactosamine-induced lethality, and this appears to be secondary to a post-receptor defect in p55 TNF receptor signaling. The studies confirm an essential role for TNF-alpha and p55 TNF receptor signaling in the hepatocyte apoptosis and lethality associated with lipopolysaccharide and D-galactosamine administration.
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| pubmed:grant | |
| pubmed:language |
eng
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| pubmed:journal | |
| pubmed:citationSubset |
IM
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| pubmed:chemical |
http://linkedlifedata.com/resource/pubmed/chemical/CASP3 protein, human,
http://linkedlifedata.com/resource/pubmed/chemical/Casp3 protein, mouse,
http://linkedlifedata.com/resource/pubmed/chemical/Caspase 3,
http://linkedlifedata.com/resource/pubmed/chemical/Caspases,
http://linkedlifedata.com/resource/pubmed/chemical/Galactosamine,
http://linkedlifedata.com/resource/pubmed/chemical/Lipopolysaccharides,
http://linkedlifedata.com/resource/pubmed/chemical/Recombinant Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/Tumor Necrosis Factor-alpha
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| pubmed:status |
MEDLINE
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| pubmed:issn |
0968-0519
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| pubmed:author | |
| pubmed:issnType |
Print
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| pubmed:volume |
7
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| pubmed:owner |
NLM
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| pubmed:authorsComplete |
Y
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| pubmed:pagination |
375-80
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| pubmed:dateRevised |
2009-11-19
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| pubmed:meshHeading |
pubmed-meshheading:11753206-Animals,
pubmed-meshheading:11753206-Apoptosis,
pubmed-meshheading:11753206-Caspase 3,
pubmed-meshheading:11753206-Caspases,
pubmed-meshheading:11753206-Drug Therapy, Combination,
pubmed-meshheading:11753206-Drug-Induced Liver Injury,
pubmed-meshheading:11753206-Galactosamine,
pubmed-meshheading:11753206-Humans,
pubmed-meshheading:11753206-Lipopolysaccharides,
pubmed-meshheading:11753206-Liver,
pubmed-meshheading:11753206-Liver Diseases,
pubmed-meshheading:11753206-Longevity,
pubmed-meshheading:11753206-Mice,
pubmed-meshheading:11753206-Mice, Inbred C57BL,
pubmed-meshheading:11753206-Mice, Inbred NOD,
pubmed-meshheading:11753206-Mice, Knockout,
pubmed-meshheading:11753206-Mice, Transgenic,
pubmed-meshheading:11753206-Necrosis,
pubmed-meshheading:11753206-Recombinant Proteins,
pubmed-meshheading:11753206-Species Specificity,
pubmed-meshheading:11753206-Tumor Necrosis Factor-alpha
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| pubmed:year |
2001
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| pubmed:articleTitle |
Genetic determinants of lipopolysaccharide and D-galactosamine-mediated hepatocellular apoptosis and lethality.
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| pubmed:affiliation |
Department of Surgery, University of Florida College of Medicine Gainesville, Florida 32610, USA.
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| pubmed:publicationType |
Journal Article,
Research Support, U.S. Gov't, P.H.S.
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