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rdf:type |
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lifeskim:mentions |
umls-concept:C0007578,
umls-concept:C0017262,
umls-concept:C0026844,
umls-concept:C0034693,
umls-concept:C0034721,
umls-concept:C0052460,
umls-concept:C0185117,
umls-concept:C0282554,
umls-concept:C0971150,
umls-concept:C1135918,
umls-concept:C1527240,
umls-concept:C2911684
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pubmed:issue |
2
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pubmed:dateCreated |
2006-12-12
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pubmed:abstractText |
Vascular inflammation induced by the proinflammatory cytokine/NF-kappaB pathway is one of the key mechanisms in the development of atherosclerosis. Peroxisome proliferators-activated receptor-gamma (PPARgamma) plays an important role in the prevention of arterial inflammation and formation of atherogenesis. Herein we examine the effects of a newly identified synthetic PPARgamma ligand, ascochlorin-6 (AS-6), on TNF-alpha-stimulated NF-kappaB activity and inflammatory molecule expression in vascular smooth muscle cells (VSMCs). AS-6 successfully inhibited TNF-alpha-stimulated NF-kappaB activity and inflammatory molecule expression, including vascular cell adhesion molecule-1 (VCAM-1), monocyte chemotactic protein-1 (MCP-1), and fractalkine (CX3CL1). Transient transfection with an [NF-kappaB]x4 luciferase reporter construct showed that AS-6 inhibition of TNF-alpha-stimulated NF-kappaB activation was PPARgamma-dependent. The effects of AS-6 on TNF-alpha-stimulated VCAM-1 and CX3CL1 expression were abolished in cells transfected with an adenovirus expressing dominant-negative PPARgamma and in cells treated with a PPARgamma specific inhibitor, GW9662, confirming again that the anti-inflammatory effect of AS-6 was PPARgamma-dependent. The inhibitory effects of AS-6 on TNF-alpha-stimulated inflammatory gene expression and NF-kappaB activation were more potent than those of rosiglitazone and pioglitazone. This study shows that AS-6 reduces the inflammatory response to TNF-alpha in VSMCs. The data suggest the possibility that AS-6 can be used to prevent the development and progression of atherosclerosis.
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pubmed:language |
eng
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pubmed:journal |
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pubmed:citationSubset |
IM
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pubmed:chemical |
http://linkedlifedata.com/resource/pubmed/chemical/4-O-carboxymethylascochlorin,
http://linkedlifedata.com/resource/pubmed/chemical/Alkenes,
http://linkedlifedata.com/resource/pubmed/chemical/Ccl2 protein, rat,
http://linkedlifedata.com/resource/pubmed/chemical/Chemokine CCL2,
http://linkedlifedata.com/resource/pubmed/chemical/Chemokine CX3CL1,
http://linkedlifedata.com/resource/pubmed/chemical/Chemokines, CX3C,
http://linkedlifedata.com/resource/pubmed/chemical/Cx3cl1 protein, rat,
http://linkedlifedata.com/resource/pubmed/chemical/Glycolates,
http://linkedlifedata.com/resource/pubmed/chemical/Ligands,
http://linkedlifedata.com/resource/pubmed/chemical/Membrane Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/NF-kappa B,
http://linkedlifedata.com/resource/pubmed/chemical/PPAR gamma,
http://linkedlifedata.com/resource/pubmed/chemical/Phenols,
http://linkedlifedata.com/resource/pubmed/chemical/Recombinant Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/Tumor Necrosis Factor-alpha,
http://linkedlifedata.com/resource/pubmed/chemical/Vascular Cell Adhesion Molecule-1,
http://linkedlifedata.com/resource/pubmed/chemical/ascochlorin
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pubmed:status |
MEDLINE
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pubmed:month |
Dec
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pubmed:issn |
0024-3205
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pubmed:author |
pubmed-author:AndoKunioK,
pubmed-author:ChangYoung-ChaeYC,
pubmed-author:KimHye-SoonHS,
pubmed-author:KimKwon-BaeKB,
pubmed-author:KimYoon-NyunYN,
pubmed-author:LeeIn-KyuIK,
pubmed-author:LeeKi-UpKU,
pubmed-author:LeeKyeong-MinKM,
pubmed-author:MagaeJunjiJ,
pubmed-author:ParkJoong-YeolJY,
pubmed-author:ParkKeun-GyuKG
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pubmed:issnType |
Print
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pubmed:day |
14
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pubmed:volume |
80
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
120-6
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pubmed:dateRevised |
2007-11-15
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pubmed:meshHeading |
pubmed-meshheading:16989870-Adenoviridae,
pubmed-meshheading:16989870-Alkenes,
pubmed-meshheading:16989870-Animals,
pubmed-meshheading:16989870-Aorta, Thoracic,
pubmed-meshheading:16989870-Blotting, Northern,
pubmed-meshheading:16989870-Blotting, Western,
pubmed-meshheading:16989870-Cells, Cultured,
pubmed-meshheading:16989870-Chemokine CCL2,
pubmed-meshheading:16989870-Chemokine CX3CL1,
pubmed-meshheading:16989870-Chemokines, CX3C,
pubmed-meshheading:16989870-Gene Expression,
pubmed-meshheading:16989870-Genetic Vectors,
pubmed-meshheading:16989870-Glycolates,
pubmed-meshheading:16989870-Ligands,
pubmed-meshheading:16989870-Male,
pubmed-meshheading:16989870-Membrane Proteins,
pubmed-meshheading:16989870-Muscle, Smooth, Vascular,
pubmed-meshheading:16989870-NF-kappa B,
pubmed-meshheading:16989870-PPAR gamma,
pubmed-meshheading:16989870-Phenols,
pubmed-meshheading:16989870-Rats,
pubmed-meshheading:16989870-Rats, Sprague-Dawley,
pubmed-meshheading:16989870-Recombinant Proteins,
pubmed-meshheading:16989870-Transfection,
pubmed-meshheading:16989870-Tumor Necrosis Factor-alpha,
pubmed-meshheading:16989870-Vascular Cell Adhesion Molecule-1
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pubmed:year |
2006
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pubmed:articleTitle |
The ascochlorin derivative, AS-6, inhibits TNF-alpha-induced adhesion molecule and chemokine expression in rat vascular smooth muscle cells.
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pubmed:affiliation |
Department of Internal Medicine and Institute for Medical Science, Keimyung University School of Medicine, Daegu, South Korea.
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pubmed:publicationType |
Journal Article,
Research Support, Non-U.S. Gov't
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