Linked Life Data

15368307

Source:http://linkedlifedata.com/resource/pubmed/id/15368307

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
10
pubmed:dateCreated
2004-9-15
pubmed:abstractText
T cell-mediated hepatitis is associated with significant morbidity and mortality worldwide. Levels of C-C chemokine ligand 3/macrophage inflammatory protein-1alpha (CCL3/MIP-1alpha) are elevated in the serum of patients with T cell-mediated liver diseases, but its role is not fully understood. Con A-induced hepatitis is a murine liver-specific inflammation mediated by activated T cells and is driven by an up-regulation of the hepatic expression of IFN-gamma. In this study, we have used CCL3/MIP-1alpha gene-deficient mice to examine the role of CCL3/MIP-1alpha in the pathogenesis of Con A-induced hepatitis. We demonstrate a novel pro-inflammatory role for CCL3/MIP-1alpha since CCL3/MIP-1alpha deficiency significantly attenuated hepatic injury, both biochemically and histologically. Moreover, the recruitment of CCR1-expressing CD4(+) T cells to the liver after Con A treatment was strikingly attenuated by CCL3/MIP-1alpha deficiency. Correspondingly, hepatic IFN-gamma produced by the recruited CD4(+) T cells was significantly reduced by CCL3/MIP-1alpha deficiency during Con A-induced hepatitis. Furthermore, treatment of mice with a dual CCR1/CCR5 peptide antagonist, methionylated RANTES, also markedly reduced hepatic injury and decreased the numbers of CD4(+) T cells within the liver producing IFN-gamma during Con A-induced hepatitis. These findings demonstrate that blockade of the CCL3/MIP-1alpha-CCR1 pathway may represent a novel therapeutic target for treating T cell-mediated liver diseases.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Oct
pubmed:issn
0014-2980
pubmed:author
pubmed:issnType
Print
pubmed:volume
34
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
2907-18
pubmed:dateRevised
2009-11-19
pubmed:meshHeading
pubmed-meshheading:15368307-Animals, pubmed-meshheading:15368307-CD4-Positive T-Lymphocytes, pubmed-meshheading:15368307-Chemokine CCL3, pubmed-meshheading:15368307-Chemokine CCL4, pubmed-meshheading:15368307-Chemokine CCL5, pubmed-meshheading:15368307-Concanavalin A, pubmed-meshheading:15368307-Disease Models, Animal, pubmed-meshheading:15368307-Drug-Induced Liver Injury, pubmed-meshheading:15368307-Flow Cytometry, pubmed-meshheading:15368307-Fluorescent Antibody Technique, pubmed-meshheading:15368307-Interferon-gamma, pubmed-meshheading:15368307-Liver, pubmed-meshheading:15368307-Macrophage Inflammatory Proteins, pubmed-meshheading:15368307-Male, pubmed-meshheading:15368307-Mice, pubmed-meshheading:15368307-Mice, Knockout, pubmed-meshheading:15368307-Neutrophil Infiltration, pubmed-meshheading:15368307-Receptors, CCR1, pubmed-meshheading:15368307-Receptors, CCR5, pubmed-meshheading:15368307-Receptors, Chemokine
pubmed:year
2004
pubmed:articleTitle
CCL3/MIP-1alpha is pro-inflammatory in murine T cell-mediated hepatitis by recruiting CCR1-expressing CD4(+) T cells to the liver.
pubmed:affiliation
Liver Unit, Gastrointestinal Research Group, Faculty of Medicine, University of Calgary, Calgary, Alberta, Canada.
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't