Linked Life Data

16025512

Source:http://linkedlifedata.com/resource/pubmed/id/16025512

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
2
pubmed:dateCreated
2005-7-21
pubmed:abstractText
The CD154-CD40 interaction is a critical costimulatory pathway modulating the cellular immune response. Moreover, fulminant hepatitis of various etiologies is characterized by a hepatic influx of CD154-expressing T cells and an upregulation of CD40 expression on Kupffer cells and hepatocytes, implicating this pathway in the pathogenesis of fulminant hepatitis. In this study, we used a murine model of fulminant hepatitis induced by concanavalin A (con A) and documented a significant influx of CD154-expressing T cells into the livers of mice treated with con A, in association with markedly increased expression of CD40 restricted mainly to hepatocytes in damaged areas of the liver. Furthermore, con A hepatitis in CD154-deficient mice was significantly attenuated compared with that in wild-type controls and was associated with a decrease in hepatic tumor necrosis factor alpha (TNF-alpha) levels and hepatocyte death. We next determined the role of the CD154-CD40 pathway in hepatocyte death in vitro. These in vitro studies demonstrated that TNF-alpha induces CD40 expression in hepatocytes and that subsequent activation of CD40 results in hepatocyte apoptosis mediated at least in part by enhanced hepatocyte expression of FasL. In conclusion, CD154 stimulation of CD40 plays a central role in hepatocyte death in fulminant hepatitis through direct and indirect pathways that may have direct therapeutic implications in humans. Supplementary material for this article can be found on the HEPATOLOGY website (http://interscience.wiley.com/jpages/0270-9139/suppmat/index.html).
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Aug
pubmed:issn
0270-9139
pubmed:author
pubmed:issnType
Print
pubmed:volume
42
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
372-80
pubmed:dateRevised
2006-11-15
pubmed:meshHeading
pubmed:year
2005
pubmed:articleTitle
CD154-CD40 interactions drive hepatocyte apoptosis in murine fulminant hepatitis.
pubmed:affiliation
Liver Unit, Faculty of Medicine, University of Calgary, 3330 Hospital Drive NW, Calgary, Alberta T2N 4N1, Canada.
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't