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rdf:type |
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lifeskim:mentions |
umls-concept:C0079904,
umls-concept:C0225336,
umls-concept:C0332120,
umls-concept:C0851285,
umls-concept:C0871261,
umls-concept:C1704632,
umls-concept:C1706817,
umls-concept:C2348867,
umls-concept:C2587213,
umls-concept:C2728259,
umls-concept:C2911692
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pubmed:issue |
16
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pubmed:dateCreated |
2005-9-22
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pubmed:abstractText |
Activation of the transcription factor NF-kappaB is critical for the tumor necrosis factor-alpha (TNF-alpha)-induced inflammatory response. Here we report the complete gene expression profile from activated microvascular endothelial cells emphasizing the direct contribution of the NF-kappaB pathway. Human microvascular endothelial cell line-1 (HMEC-1) cells were modified to express dominant interfering mutants of the IKK/NF-kappaB signaling module and expression profiles were determined. Our results provide compelling evidence for the virtually absolute dependence of TNF-alpha-regulated genes on NF-kappaB. A constitutively active IKK2 was sufficient for maximal induction of most target genes, whereas a transdominant IkappaBalpha suppressed gene expression. Several genes with a critical role in atherogenesis were identified. The endothelial lipase (EL) gene, a key enzyme involved in lipoprotein metabolism, was investigated more in detail. Binding sites interacting with NF-kappaB in vitro and in vivo were identified and co-transfection experiments demonstrated the direct regulation of the EL promoter by NF-kappaB. We conclude that targeting the IKK/NF-kappaB pathway or specific genes downstream may be effective for the control or prevention of chronic inflammatory diseases such as atherosclerosis.
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pubmed:commentsCorrections |
http://linkedlifedata.com/resource/pubmed/commentcorrection/16177180-10192396,
http://linkedlifedata.com/resource/pubmed/commentcorrection/16177180-10318835,
http://linkedlifedata.com/resource/pubmed/commentcorrection/16177180-10602461,
http://linkedlifedata.com/resource/pubmed/commentcorrection/16177180-10766741,
http://linkedlifedata.com/resource/pubmed/commentcorrection/16177180-10837071,
http://linkedlifedata.com/resource/pubmed/commentcorrection/16177180-11337506,
http://linkedlifedata.com/resource/pubmed/commentcorrection/16177180-11694538,
http://linkedlifedata.com/resource/pubmed/commentcorrection/16177180-11743587,
http://linkedlifedata.com/resource/pubmed/commentcorrection/16177180-11931769,
http://linkedlifedata.com/resource/pubmed/commentcorrection/16177180-11983155,
http://linkedlifedata.com/resource/pubmed/commentcorrection/16177180-12121660,
http://linkedlifedata.com/resource/pubmed/commentcorrection/16177180-12482940,
http://linkedlifedata.com/resource/pubmed/commentcorrection/16177180-12490957,
http://linkedlifedata.com/resource/pubmed/commentcorrection/16177180-12490960,
http://linkedlifedata.com/resource/pubmed/commentcorrection/16177180-12569161,
http://linkedlifedata.com/resource/pubmed/commentcorrection/16177180-12609972,
http://linkedlifedata.com/resource/pubmed/commentcorrection/16177180-12639996,
http://linkedlifedata.com/resource/pubmed/commentcorrection/16177180-12810721,
http://linkedlifedata.com/resource/pubmed/commentcorrection/16177180-1361507,
http://linkedlifedata.com/resource/pubmed/commentcorrection/16177180-14522944,
http://linkedlifedata.com/resource/pubmed/commentcorrection/16177180-14715628,
http://linkedlifedata.com/resource/pubmed/commentcorrection/16177180-14993123,
http://linkedlifedata.com/resource/pubmed/commentcorrection/16177180-15053878,
http://linkedlifedata.com/resource/pubmed/commentcorrection/16177180-15084260,
http://linkedlifedata.com/resource/pubmed/commentcorrection/16177180-15218148,
http://linkedlifedata.com/resource/pubmed/commentcorrection/16177180-15226448,
http://linkedlifedata.com/resource/pubmed/commentcorrection/16177180-15284123,
http://linkedlifedata.com/resource/pubmed/commentcorrection/16177180-15304490,
http://linkedlifedata.com/resource/pubmed/commentcorrection/16177180-15314694,
http://linkedlifedata.com/resource/pubmed/commentcorrection/16177180-15536134,
http://linkedlifedata.com/resource/pubmed/commentcorrection/16177180-7692309,
http://linkedlifedata.com/resource/pubmed/commentcorrection/16177180-8551575,
http://linkedlifedata.com/resource/pubmed/commentcorrection/16177180-9572988,
http://linkedlifedata.com/resource/pubmed/commentcorrection/16177180-9691094
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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/CHUK protein, human,
http://linkedlifedata.com/resource/pubmed/chemical/Cytoskeletal Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/I-kappa B Kinase,
http://linkedlifedata.com/resource/pubmed/chemical/IKBKB protein, human,
http://linkedlifedata.com/resource/pubmed/chemical/IKBKE protein, human,
http://linkedlifedata.com/resource/pubmed/chemical/Inflammation Mediators,
http://linkedlifedata.com/resource/pubmed/chemical/LIPG protein, human,
http://linkedlifedata.com/resource/pubmed/chemical/Lipase,
http://linkedlifedata.com/resource/pubmed/chemical/NF-kappa B,
http://linkedlifedata.com/resource/pubmed/chemical/PPL protein, human,
http://linkedlifedata.com/resource/pubmed/chemical/Plakins,
http://linkedlifedata.com/resource/pubmed/chemical/Protein-Serine-Threonine Kinases,
http://linkedlifedata.com/resource/pubmed/chemical/Transcription Factor RelA,
http://linkedlifedata.com/resource/pubmed/chemical/Tumor Necrosis Factor-alpha
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pubmed:status |
MEDLINE
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pubmed:issn |
1362-4962
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pubmed:author |
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pubmed:issnType |
Electronic
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pubmed:volume |
33
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
5308-19
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pubmed:dateRevised |
2009-11-19
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pubmed:meshHeading |
pubmed-meshheading:16177180-Arteriosclerosis,
pubmed-meshheading:16177180-Cell Line,
pubmed-meshheading:16177180-Cells, Cultured,
pubmed-meshheading:16177180-Cytoskeletal Proteins,
pubmed-meshheading:16177180-Endothelial Cells,
pubmed-meshheading:16177180-Endothelium, Vascular,
pubmed-meshheading:16177180-Gene Expression Profiling,
pubmed-meshheading:16177180-Gene Expression Regulation,
pubmed-meshheading:16177180-Humans,
pubmed-meshheading:16177180-I-kappa B Kinase,
pubmed-meshheading:16177180-Inflammation Mediators,
pubmed-meshheading:16177180-Lipase,
pubmed-meshheading:16177180-Mutation,
pubmed-meshheading:16177180-NF-kappa B,
pubmed-meshheading:16177180-Plakins,
pubmed-meshheading:16177180-Promoter Regions, Genetic,
pubmed-meshheading:16177180-Protein-Serine-Threonine Kinases,
pubmed-meshheading:16177180-Signal Transduction,
pubmed-meshheading:16177180-Transcription Factor RelA,
pubmed-meshheading:16177180-Tumor Necrosis Factor-alpha
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pubmed:year |
2005
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pubmed:articleTitle |
NF-kappaB controls the global pro-inflammatory response in endothelial cells: evidence for the regulation of a pro-atherogenic program.
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