Source:http://linkedlifedata.com/resource/pubmed/id/12237332
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| Predicate | Object |
|---|---|
| rdf:type | |
| lifeskim:mentions | |
| pubmed:issue |
4
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| pubmed:dateCreated |
2002-9-18
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| pubmed:abstractText |
Tranilast [N-(3,4-dimethoxycinnamoyl)anthranilic acid] inhibits vascular inflammation. However, the relevant anti-inflammatory mechanisms are not completely understood. We studied the effects of tranilast on nuclear factor-kappaB (NF-kappaB)-dependent endothelial cell adhesion molecule expression and transcriptional regulation. Cultured human umbilical vein endothelial cells were preincubated with 12.5 to 100 microg/ml tranilast. Tumor necrosis factor-alpha (TNF-alpha)-induced endothelial VCAM-1, ICAM-1, and E-selectin surface expression was inhibited dose dependently. Maximal inhibition achieved with 100 microg/ml tranilast was 38 +/- 6.9, 31.8 +/- 1.5, and 31.9 +/- 1.9%, respectively (mean +/- S.E.M., p < 0.001, n = 5). Secretion of interleukin 6, which is also NF-kappaB-sensitive, was significantly inhibited by tranilast. Endothelial MHC-I expression, which is independent of NF-kappaB, was not inhibited. Although cytokine-induced degradation of NF-kappaB inhibitor proteins (IkappaB-alpha, -beta, and -epsilon), nuclear translocation of NF-kappaB, and binding of NF-kappaB to kappaB cis-acting elements in the adhesion molecule promoters were not affected by tranilast, ICAM-1-kappaB and E-selectin-kappaB reporter gene activity was inhibited by 53% (n = 5, p < 0.01) and 51% (n = 5, p < 0.001), respectively. In contrast, using SP-1 and C/EBP constructs, reporter gene activity was not altered. Expression of the transcriptional coactivator cAMP response element binding protein binding protein (CBP) was inhibited by tranilast, resulting in a loss of interaction between NF-kappaB and CBP. Therefore, in therapeutically relevant concentrations (50 microg/ml), tranilast inhibits NF-kappaB-dependent transcriptional activation by interfering with the NF-kappaB/CBP association. We propose that inhibition of NF-kappaB dependent gene transcription contributes to the anti-inflammatory effects of tranilast.
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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/Activating Transcription Factor 1,
http://linkedlifedata.com/resource/pubmed/chemical/Anthranilic Acids,
http://linkedlifedata.com/resource/pubmed/chemical/Cell Adhesion Molecules,
http://linkedlifedata.com/resource/pubmed/chemical/Cytokines,
http://linkedlifedata.com/resource/pubmed/chemical/DNA,
http://linkedlifedata.com/resource/pubmed/chemical/DNA-Binding Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/I-kappa B Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/Ligases,
http://linkedlifedata.com/resource/pubmed/chemical/NF-kappa B,
http://linkedlifedata.com/resource/pubmed/chemical/Transcription Factors,
http://linkedlifedata.com/resource/pubmed/chemical/Tumor Necrosis Factor-alpha,
http://linkedlifedata.com/resource/pubmed/chemical/guanosine 3',5'-polyphosphate...,
http://linkedlifedata.com/resource/pubmed/chemical/tranilast
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| pubmed:status |
MEDLINE
|
| pubmed:month |
Oct
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| pubmed:issn |
0026-895X
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| pubmed:author | |
| pubmed:issnType |
Print
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| pubmed:volume |
62
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| pubmed:owner |
NLM
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| pubmed:authorsComplete |
Y
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| pubmed:pagination |
856-63
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| pubmed:dateRevised |
2006-11-15
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| pubmed:meshHeading |
pubmed-meshheading:12237332-Activating Transcription Factor 1,
pubmed-meshheading:12237332-Active Transport, Cell Nucleus,
pubmed-meshheading:12237332-Anthranilic Acids,
pubmed-meshheading:12237332-Cell Adhesion Molecules,
pubmed-meshheading:12237332-Cells, Cultured,
pubmed-meshheading:12237332-Cytokines,
pubmed-meshheading:12237332-DNA,
pubmed-meshheading:12237332-DNA-Binding Proteins,
pubmed-meshheading:12237332-Dimerization,
pubmed-meshheading:12237332-Endothelium, Vascular,
pubmed-meshheading:12237332-Humans,
pubmed-meshheading:12237332-I-kappa B Proteins,
pubmed-meshheading:12237332-Ligases,
pubmed-meshheading:12237332-NF-kappa B,
pubmed-meshheading:12237332-Transcription, Genetic,
pubmed-meshheading:12237332-Transcription Factors,
pubmed-meshheading:12237332-Tumor Necrosis Factor-alpha
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| pubmed:year |
2002
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| pubmed:articleTitle |
Tranilast inhibits cytokine-induced nuclear factor kappaB activation in vascular endothelial cells.
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| pubmed:affiliation |
Department of Medicine II, University of Bochum, Bochum, Germany. martin.spieker@ruhr.uni-bochum.de
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| pubmed:publicationType |
Journal Article,
Research Support, Non-U.S. Gov't
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