Source:http://linkedlifedata.com/resource/pubmed/id/15224143
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Predicate | Object |
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rdf:type | |
lifeskim:mentions | |
pubmed:issue |
3
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pubmed:dateCreated |
2004-6-29
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pubmed:abstractText |
To investigate the inhibition of cyclosporin A (CsA) on neutrophil adhesion to human umbilical vein endothelial cells (HUVECs, ECV-304) induced by hypoxia/reoxygenation and further explore its mechanism, a 1 h hypoxia/4 h reoxygenation model was reproduced using ECV-304. The adhesion rate of neutrophils to ECV-304 was determined by measuring the activity of endogenous hexosaminidase. The expression of endothelial cell adhesion molecules of E-selectin and ICAM-1 was measured by flow cytometry. The expression of cyclophilin A (CyPA) and the activation of ERK1/2 was compared among experimental groups by Western blot. The content of reactive oxygen species (ROS) was measured by Fenton reaction. After being stimulated with 1 h hypoxia/4 h reoxygenation, ECV-304 showed an enhanced neutrophil adhensiveness in association with an increased surface expression of E-selectin and ICAM-1. In parallel, the content of ROS was also increased. These effects were significantly suppressed by the addition of CsA. Most importantly, the expression of CyPA was significantly increased following 1 h hypoxia/4 h reoxygenation, which was accompanied with an increased activation of ERK1/2. Treatment with CyPA inhibitor CsA and CyPA antisense oligonucleotides significantly inhibited the activation of ERK1/2 and decreased the adhesion of neutrophils to ECV-304. The specific ERK1/2 inhibitor PD98059 caused an inhibition of neutrophil adhesion to hypoxia/reoxygenation-stimulated ECV-304. Our data confirm that CsA inhibits neutrophil adhesion to hypoxia/reoxygenation stimulated ECV-304 by a mechanism involving inhibition of the signal transduction of ROS, CyPA and ERK1/2.
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pubmed:language |
chi
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pubmed:journal | |
pubmed:citationSubset |
IM
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pubmed:chemical |
http://linkedlifedata.com/resource/pubmed/chemical/Cyclophilins,
http://linkedlifedata.com/resource/pubmed/chemical/Cyclosporine,
http://linkedlifedata.com/resource/pubmed/chemical/Intercellular Adhesion Molecule-1,
http://linkedlifedata.com/resource/pubmed/chemical/Mitogen-Activated Protein Kinase 1,
http://linkedlifedata.com/resource/pubmed/chemical/Mitogen-Activated Protein Kinase 3,
http://linkedlifedata.com/resource/pubmed/chemical/Reactive Oxygen Species
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pubmed:status |
MEDLINE
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pubmed:month |
Jun
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pubmed:issn |
0371-0874
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pubmed:author | |
pubmed:issnType |
Print
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pubmed:day |
25
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pubmed:volume |
56
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
313-20
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pubmed:dateRevised |
2009-11-19
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pubmed:meshHeading |
pubmed-meshheading:15224143-Cell Adhesion,
pubmed-meshheading:15224143-Cell Hypoxia,
pubmed-meshheading:15224143-Cells, Cultured,
pubmed-meshheading:15224143-Cyclophilins,
pubmed-meshheading:15224143-Cyclosporine,
pubmed-meshheading:15224143-Endothelium, Vascular,
pubmed-meshheading:15224143-Humans,
pubmed-meshheading:15224143-Intercellular Adhesion Molecule-1,
pubmed-meshheading:15224143-Mitogen-Activated Protein Kinase 1,
pubmed-meshheading:15224143-Mitogen-Activated Protein Kinase 3,
pubmed-meshheading:15224143-Neutrophils,
pubmed-meshheading:15224143-Reactive Oxygen Species,
pubmed-meshheading:15224143-Reperfusion Injury,
pubmed-meshheading:15224143-Signal Transduction,
pubmed-meshheading:15224143-Umbilical Veins
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pubmed:year |
2004
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pubmed:articleTitle |
[Cyclosporin A inhibits the adhesion of neutrophil with ECV-304 induced by hypoxia/reoxygenation via ROS-Cyclophilin A-ERK1/2 pathway].
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pubmed:affiliation |
Institute of Pharmacy and Pharmacology, Nanhua University, Hengyang, Hunan 421001, China.
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pubmed:publicationType |
Journal Article,
English Abstract,
Research Support, Non-U.S. Gov't
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