Source:http://linkedlifedata.com/resource/pubmed/id/10826501
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rdf:type | |
lifeskim:mentions |
umls-concept:C0021760,
umls-concept:C0026844,
umls-concept:C0030685,
umls-concept:C0040648,
umls-concept:C0079281,
umls-concept:C0079904,
umls-concept:C0086418,
umls-concept:C0205263,
umls-concept:C0391871,
umls-concept:C0680255,
umls-concept:C1135918,
umls-concept:C1283071,
umls-concept:C1879547,
umls-concept:C1963578
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pubmed:issue |
2
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pubmed:dateCreated |
2000-9-7
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pubmed:abstractText |
The potent vasoconstrictor peptide endothelin-1 (ET-1) has been implicated in the pathophysiology of atherosclerosis and its complications. Since inflammation of the vessel wall is a hallmark of atherosclerosis, the purpose of the present study was to investigate the influence of ET-1 on cytokine production in human vascular smooth muscle cells (SMC) as a marker of inflammatory cell activation. ET-1 (100 pM - 1 microM) stimulated interleukin-6 (IL-6) secretion from human vascular SMC in a concentration-dependent manner. The ET-A-receptor antagonist BQ-123 (10 microM), but not the ET-B-receptor antagonist BQ-788, inhibited IL-6 release. ET-1 also transiently increased IL-6 mRNA compatible with regulation of IL-6 release at the pretranslational level. Electrophoretic mobility shift assays demonstrated time- and concentration-dependent activation of the proinflammatory transcription factor nuclear factor-kappaB (NF-kappaB) in ET-1-stimulated human vascular SMC. A decoy oligodeoxynucleotide bearing the NF-kappaB binding site inhibited ET-1-stimulated IL-6 release to a great extent suggesting that this transcription factor plays a key role for cytokine production elicited by ET-1. Moreover, the antioxidant pyrrolidine dithiocarbamate (10 microM) inhibited ET-1-induced IL-6 release indicating involvement of reactive oxygen species in ET-1 signaling. ET-1-stimulated IL-6 secretion was also suppressed by diphenylene iodonium (40 microM), an inhibitor of flavon-containing enzymes such as NADH/NADPH oxidase. The results demonstrate the ability of ET-1 to induce an inflammatory response in human vascular SMC. These observations may contribute to a better understanding of the role of ET-1 in inflammatory activation of the vessel wall during atherogenesis.
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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/Antioxidants,
http://linkedlifedata.com/resource/pubmed/chemical/Endothelin-1,
http://linkedlifedata.com/resource/pubmed/chemical/Interleukin-6,
http://linkedlifedata.com/resource/pubmed/chemical/NF-kappa B,
http://linkedlifedata.com/resource/pubmed/chemical/Receptor, Endothelin A,
http://linkedlifedata.com/resource/pubmed/chemical/Receptors, Endothelin
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pubmed:status |
MEDLINE
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pubmed:month |
Apr
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pubmed:issn |
0300-8428
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pubmed:author | |
pubmed:issnType |
Print
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pubmed:volume |
95
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
98-105
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pubmed:dateRevised |
2006-11-15
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pubmed:meshHeading |
pubmed-meshheading:10826501-Antioxidants,
pubmed-meshheading:10826501-Cells, Cultured,
pubmed-meshheading:10826501-Endothelin-1,
pubmed-meshheading:10826501-Humans,
pubmed-meshheading:10826501-Interleukin-6,
pubmed-meshheading:10826501-Muscle, Smooth, Vascular,
pubmed-meshheading:10826501-NF-kappa B,
pubmed-meshheading:10826501-Receptor, Endothelin A,
pubmed-meshheading:10826501-Receptors, Endothelin
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pubmed:year |
2000
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pubmed:articleTitle |
Endothelin-1 induces interleukin-6 release via activation of the transcription factor NF-kappaB in human vascular smooth muscle cells.
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pubmed:affiliation |
Medizinische Universitätsklinik, Abt. Kardiologie, Heidelberg, Germany.
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pubmed:publicationType |
Journal Article,
Research Support, Non-U.S. Gov't
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