Source:http://linkedlifedata.com/resource/pubmed/id/17081232
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| Predicate | Object |
|---|---|
| rdf:type | |
| lifeskim:mentions | |
| pubmed:issue |
12
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| pubmed:dateCreated |
2006-11-3
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| pubmed:abstractText |
Janus kinase 3 (JAK3) mediates signal transduction from cytokine receptors using the common gamma chain. The rationally designed inhibitor of JAK3, CP-690,550, prevents acute allograft rejection in rodents and in nonhuman primates. Here we investigated the ability of CP-690,550, to prevent allograft vasculopathy in a rodent model of aorta transplantation. Aortas from AxC Irish (RT1(a)) or Lewis (RT1(l)) rats were heterotopically transplanted into the infra-renal aorta of Lewis recipients and harvested at 28 or 56 days. Treated recipients received CP-690,550 by osmotic pumps (mean drug exposure of 110 +/- 38 ng/ml). Significant intimal hyperplasia was demonstrated in untreated allografts when compared with isografts at 28 days (2.08 +/- 0.85% vs. 0.43 +/- 0.2% luminal obliteration, respectively, P = 0.001) and 56 days (5.3 +/- 2.4% vs. 0.38 +/- 0.3%, P = 0.002). Treatment caused a 51% reduction in intimal hyperplasia at day 56. CP-690,550-treated animals also had a significant reduction of donor-specific IgG production and of the gene expression for suppressor of cytokine signaling-3 and with unchanged levels of expression of RANTES, IP-10 and transforming growth factor-beta1. These results are the first to show that JAK3 blockade by CP-690,550 effectively prevents allograft vasculopathy in this rat model of aorta transplantation.
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| pubmed:language |
eng
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| pubmed:journal | |
| pubmed:citationSubset |
IM
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| pubmed:chemical |
http://linkedlifedata.com/resource/pubmed/chemical/Chemokine CCL5,
http://linkedlifedata.com/resource/pubmed/chemical/Interferon-gamma,
http://linkedlifedata.com/resource/pubmed/chemical/Janus Kinase 3,
http://linkedlifedata.com/resource/pubmed/chemical/Protein Kinase Inhibitors,
http://linkedlifedata.com/resource/pubmed/chemical/Pyrimidines,
http://linkedlifedata.com/resource/pubmed/chemical/Pyrroles,
http://linkedlifedata.com/resource/pubmed/chemical/Socs3 protein, rat,
http://linkedlifedata.com/resource/pubmed/chemical/Suppressor of Cytokine Signaling...,
http://linkedlifedata.com/resource/pubmed/chemical/tofacitinib
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| pubmed:status |
MEDLINE
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| pubmed:month |
Dec
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| pubmed:issn |
0934-0874
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| pubmed:author | |
| pubmed:issnType |
Print
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| pubmed:volume |
19
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| pubmed:owner |
NLM
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| pubmed:authorsComplete |
Y
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| pubmed:pagination |
1014-21
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| pubmed:dateRevised |
2011-11-17
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| pubmed:meshHeading |
pubmed-meshheading:17081232-Animals,
pubmed-meshheading:17081232-Aorta,
pubmed-meshheading:17081232-Arteriosclerosis,
pubmed-meshheading:17081232-Chemokine CCL5,
pubmed-meshheading:17081232-Hyperplasia,
pubmed-meshheading:17081232-Interferon-gamma,
pubmed-meshheading:17081232-Janus Kinase 3,
pubmed-meshheading:17081232-Killer Cells, Natural,
pubmed-meshheading:17081232-Male,
pubmed-meshheading:17081232-Protein Kinase Inhibitors,
pubmed-meshheading:17081232-Pyrimidines,
pubmed-meshheading:17081232-Pyrroles,
pubmed-meshheading:17081232-Rats,
pubmed-meshheading:17081232-Rats, Inbred ACI,
pubmed-meshheading:17081232-Rats, Inbred Lew,
pubmed-meshheading:17081232-Suppressor of Cytokine Signaling Proteins,
pubmed-meshheading:17081232-Transplantation, Homologous,
pubmed-meshheading:17081232-Tunica Intima
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| pubmed:year |
2006
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| pubmed:articleTitle |
Janus kinase 3 inhibition with CP-690,550 prevents allograft vasculopathy.
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| pubmed:affiliation |
Transplantation Immunology Laboratory, Department of Cardiothoracic Surgery, Falk Cardiovascular Research Center, Stanford University School of Medicine, Stanford, CA 94305-5407, USA.
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| pubmed:publicationType |
Journal Article,
Research Support, Non-U.S. Gov't
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