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pubmed-article:15224143pubmed:abstractTextTo 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.lld:pubmed
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pubmed-article:15224143pubmed:authorpubmed-author:YanFeng-Xiang...lld:pubmed
pubmed-article:15224143pubmed:authorpubmed-author:LiaoDuan-Fang...lld:pubmed
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pubmed-article:15224143pubmed:pagination313-20lld:pubmed
pubmed-article:15224143pubmed:dateRevised2009-11-19lld:pubmed
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pubmed-article:15224143pubmed:articleTitle[Cyclosporin A inhibits the adhesion of neutrophil with ECV-304 induced by hypoxia/reoxygenation via ROS-Cyclophilin A-ERK1/2 pathway].lld:pubmed
pubmed-article:15224143pubmed:affiliationInstitute of Pharmacy and Pharmacology, Nanhua University, Hengyang, Hunan 421001, China.lld:pubmed
pubmed-article:15224143pubmed:publicationTypeJournal Articlelld:pubmed
pubmed-article:15224143pubmed:publicationTypeEnglish Abstractlld:pubmed
pubmed-article:15224143pubmed:publicationTypeResearch Support, Non-U.S. Gov'tlld:pubmed