Source:http://linkedlifedata.com/resource/pubmed/id/11526540
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| Predicate | Object |
|---|---|
| rdf:type | |
| lifeskim:mentions | |
| pubmed:issue |
3
|
| pubmed:dateCreated |
2001-8-29
|
| pubmed:abstractText |
Liver resident NK1.1+ T cells are supposed to play a pivotal role in the onset of inflammatory liver injury in experimental mouse models such as concanavalin A (Con A)-induced hepatitis. These cells, expressing the adhesion receptor, CD44, are largely depleted from the liver by a single intravenous injection of low-molecular-weight fragments of hyaluronic acid (LMW-HA). Here, we report that LMW-HA pretreatment protected mice from liver injury in several models of T-cell- and macrophage-dependent, tumor necrosis factor alpha (TNF-alpha)-mediated inflammatory liver injury, i.e., from liver injury induced by either Con A or Pseudomonas exotoxin A (PEA) or PEA/lipopolysaccharide (LPS). Interestingly, apart from inhibition of cellular adhesion, pretreatment of mice with LMW-HA was also capable of preventing hepatocellular apoptosis and activation of caspase-3 induced by direct administration of recombinant murine (rmu) TNF-alpha to D-galactosamine (GalN)-sensitized mice. LMW-HA-induced hepatoprotection could be neutralized by pretreatment with the nuclear factor-kappaB (NF-kappaB) inhibitor, pyrrolidine dithiocarbamate (PDTC), demonstrating the involvement of NF-kappaB in the observed protective mechanism. Indeed, injection of LMW-HA rapidly induced the production of TNF-alpha by Kupffer cells and the translocation of NF-kappaB into hepatocellular nuclei. Both LMW-HA-induced TNF-alpha production and NF-kappaB translocation were blocked by pretreatment with PDTC. Our findings provide evidence for an unknown mechanism of LMW-HA-dependent protection from inflammatory liver disease, i.e., induction of TNF-alpha- and NF-kappaB-dependent cytoprotective proteins within the target parenchymal liver cells.
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| pubmed:language |
eng
|
| pubmed:journal | |
| pubmed:citationSubset |
IM
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| pubmed:chemical |
http://linkedlifedata.com/resource/pubmed/chemical/ADP Ribose Transferases,
http://linkedlifedata.com/resource/pubmed/chemical/Antigens, CD44,
http://linkedlifedata.com/resource/pubmed/chemical/Bacterial Toxins,
http://linkedlifedata.com/resource/pubmed/chemical/Concanavalin A,
http://linkedlifedata.com/resource/pubmed/chemical/Cytokines,
http://linkedlifedata.com/resource/pubmed/chemical/Exotoxins,
http://linkedlifedata.com/resource/pubmed/chemical/Hyaluronic Acid,
http://linkedlifedata.com/resource/pubmed/chemical/Lipopolysaccharides,
http://linkedlifedata.com/resource/pubmed/chemical/NF-kappa B,
http://linkedlifedata.com/resource/pubmed/chemical/Tumor Necrosis Factor-alpha,
http://linkedlifedata.com/resource/pubmed/chemical/Virulence Factors,
http://linkedlifedata.com/resource/pubmed/chemical/toxA protein, Pseudomonas aeruginosa
|
| pubmed:status |
MEDLINE
|
| pubmed:month |
Sep
|
| pubmed:issn |
0270-9139
|
| pubmed:author | |
| pubmed:issnType |
Print
|
| pubmed:volume |
34
|
| pubmed:owner |
NLM
|
| pubmed:authorsComplete |
Y
|
| pubmed:pagination |
535-47
|
| pubmed:dateRevised |
2009-11-19
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| pubmed:meshHeading |
pubmed-meshheading:11526540-ADP Ribose Transferases,
pubmed-meshheading:11526540-Animals,
pubmed-meshheading:11526540-Antigens, CD44,
pubmed-meshheading:11526540-Bacterial Toxins,
pubmed-meshheading:11526540-CD4 Lymphocyte Count,
pubmed-meshheading:11526540-Cell Death,
pubmed-meshheading:11526540-Concanavalin A,
pubmed-meshheading:11526540-Cytokines,
pubmed-meshheading:11526540-Drug-Induced Liver Injury,
pubmed-meshheading:11526540-Exotoxins,
pubmed-meshheading:11526540-Hyaluronic Acid,
pubmed-meshheading:11526540-Kupffer Cells,
pubmed-meshheading:11526540-Lipopolysaccharides,
pubmed-meshheading:11526540-Liver,
pubmed-meshheading:11526540-Liver Failure,
pubmed-meshheading:11526540-Lymphocyte Count,
pubmed-meshheading:11526540-Macrophages,
pubmed-meshheading:11526540-Male,
pubmed-meshheading:11526540-Mice,
pubmed-meshheading:11526540-Mice, Inbred BALB C,
pubmed-meshheading:11526540-Molecular Weight,
pubmed-meshheading:11526540-NF-kappa B,
pubmed-meshheading:11526540-T-Lymphocytes,
pubmed-meshheading:11526540-Tumor Necrosis Factor-alpha,
pubmed-meshheading:11526540-Virulence Factors
|
| pubmed:year |
2001
|
| pubmed:articleTitle |
Low-molecular-weight hyaluronic acid induces nuclear factor-kappaB-dependent resistance against tumor necrosis factor alpha-mediated liver injury in mice.
|
| pubmed:affiliation |
Institute of Experimental and Clinical Pharmacology and Toxicology, Faculty of Medicine, University of Erlangen-Nürnberg, Erlangen, Germany.
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| pubmed:publicationType |
Journal Article,
Research Support, Non-U.S. Gov't
|