Linked Life Data

14999686

Source:http://linkedlifedata.com/resource/pubmed/id/14999686

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
3
pubmed:dateCreated
2004-3-4
pubmed:abstractText
The selectin family of cell adhesion molecules is widely thought to promote inflammatory reactions by facilitating leukocyte recruitment. However, it was unexpectedly found that mice with targeted deletion of the P-selectin gene (PsKO mice) developed unpolarized type 1/type 2 cytokine responses and severely aggravated liver pathology following infection with the type 2-promoting pathogen Schistosoma mansoni. In fact, liver fibrosis, which is dependent on interleukin 13 (IL-13), increased by a factor of more than 6, despite simultaneous induction of the antifibrotic cytokine interferon gamma (IFN-gamma). Inflammation, as measured by granuloma size, also increased significantly in the absence of P-selectin. When infected PsKO mice were treated with neutralizing anti-IFN-gamma monoclonal antibodies, however, granuloma size was restored to wild-type levels; this finding revealed the potent proinflammatory role of IFN-gamma when expressed concomitantly with IL-13. Untreated PsKO mice also exhibited a significant (sixfold) reduction in decoy IL-13 receptor (IL-13 receptor alpha-2) expression when compared with infected wild-type animals. It is noteworthy, however, that when decoy receptor activity was restored in PsKO mice by treatment with soluble IL-13 receptor alpha-2-Fc, the exacerbated fibrotic response was completely inhibited. Thus, reduced expression of the decoy IL-13 receptor mediated by the elevated type 1 cytokine response probably accounts for the enhanced activity of IL-13 in PsKO mice and for the resultant increase in collagen deposition. In conclusion, the current study has revealed the critical role of P-selectin in the progression of chronic liver disease caused by schistosome parasites. By suppressing IFN-gamma and up-regulating the decoy IL-13 receptor, P-selectin dramatically inhibits the pathologic tissue remodeling that results from chronic type 2 cytokine-mediated inflammation.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Mar
pubmed:issn
0270-9139
pubmed:author
pubmed:issnType
Print
pubmed:volume
39
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
676-87
pubmed:dateRevised
2008-11-21
pubmed:meshHeading
pubmed-meshheading:14999686-Animals, pubmed-meshheading:14999686-Antibodies, Monoclonal, pubmed-meshheading:14999686-Chronic Disease, pubmed-meshheading:14999686-Cytokines, pubmed-meshheading:14999686-Eosinophilia, pubmed-meshheading:14999686-Female, pubmed-meshheading:14999686-Granuloma, Respiratory Tract, pubmed-meshheading:14999686-Hepatitis, pubmed-meshheading:14999686-Interferon-gamma, pubmed-meshheading:14999686-Interleukin-13 Receptor alpha1 Subunit, pubmed-meshheading:14999686-Liver Cirrhosis, pubmed-meshheading:14999686-Lung Diseases, pubmed-meshheading:14999686-Mice, pubmed-meshheading:14999686-Mice, Inbred C57BL, pubmed-meshheading:14999686-Mice, Knockout, pubmed-meshheading:14999686-P-Selectin, pubmed-meshheading:14999686-Protein Isoforms, pubmed-meshheading:14999686-Receptors, Interleukin, pubmed-meshheading:14999686-Receptors, Interleukin-13, pubmed-meshheading:14999686-Schistosomiasis
pubmed:year
2004
pubmed:articleTitle
P-selectin suppresses hepatic inflammation and fibrosis in mice by regulating interferon gamma and the IL-13 decoy receptor.
pubmed:affiliation
National Institute of Allergy and Infectious Diseases, National Institutes of Health, Building 50, Room 6154, MSC 8003, Bethesda, MD 20892, USA. twynn@niaid.nih.gov
pubmed:publicationType
Journal Article, Research Support, U.S. Gov't, P.H.S., Research Support, Non-U.S. Gov't