Source:http://linkedlifedata.com/resource/pubmed/id/10882039
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| Predicate | Object |
|---|---|
| rdf:type | |
| lifeskim:mentions | |
| pubmed:issue |
6
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| pubmed:dateCreated |
2000-10-19
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| pubmed:abstractText |
Glucocorticoids are potent inhibitors of cyclooxygenase-2 (prostaglandin G/H synthase-2, COX-2) expression. The focus of this work was to investigate the molecular mechanisms, by which glucocorticoids interfere with platelet-derived growth factor (PDGF)-mediated induction of COX-2 with special emphasis on the role of the transcription factors NF-kappaB/IkappaB alpha. In rat renal mesangial cells, PDGF induced a rapid and transient increase of COX-2 mRNA and protein, which reached maximal levels after 1-2 and 4 h, respectively. The in vivo half-life of COX-2 mRNA, which was estimated to be less than 1 h, was reduced by dexamethasone. Kinetic studies and COX-2 promoter activity assays indicated that dexamethasone also interfered with COX-2 transcription. Inhibition of COX-2 induction by dexamethasone was abrogated by cycloheximide, an inhibitor of translation, indicating dependence on de novo protein synthesis. As a possible mediator of dexamethasone action, the NF-kappaB/IkappaB alpha system of transcription factors was investigated. Dexamethasone doubled IkappaB alpha protein levels within 1 h and reduced complex formation of nuclear NF-kappaB proteins with DNA. Newly synthesized IkappaB alpha may thus bind to NF-kappaB and interfere with gene activation. PDGF-induced signalling, however, barely affected the NF-kappaB/IkappaB alpha system: IkappaB alpha protein remained unaltered for 30 min after treatment of mesangial cells with PDGF and was only reduced by 30% after 1 h. Concomitantly, binding of NF-kappaB proteins to DNA, detected by electrophoretic mobility shift assays, was slightly increased by 30%. Furthermore, stably transfected COX-2 promoter constructs with and without the NF-KB binding site were comparably activated by PDGF (2.5-fold increase of luciferase activity). Taken together, these data indicate that although dexamethasone interferes with the NF-kappaB/IkappaB alpha system of transcription factors, this mechanism is not essential for the inhibition of PDGF-induced COX-2 expression.
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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/Cycloheximide,
http://linkedlifedata.com/resource/pubmed/chemical/Cyclooxygenase 2,
http://linkedlifedata.com/resource/pubmed/chemical/DNA,
http://linkedlifedata.com/resource/pubmed/chemical/Dactinomycin,
http://linkedlifedata.com/resource/pubmed/chemical/Dexamethasone,
http://linkedlifedata.com/resource/pubmed/chemical/I-kappa B Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/Isoenzymes,
http://linkedlifedata.com/resource/pubmed/chemical/NF-kappa B,
http://linkedlifedata.com/resource/pubmed/chemical/Nucleic Acid Synthesis Inhibitors,
http://linkedlifedata.com/resource/pubmed/chemical/Platelet-Derived Growth Factor,
http://linkedlifedata.com/resource/pubmed/chemical/Prostaglandin-Endoperoxide Synthases,
http://linkedlifedata.com/resource/pubmed/chemical/Protein Synthesis Inhibitors,
http://linkedlifedata.com/resource/pubmed/chemical/RNA, Messenger
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| pubmed:status |
MEDLINE
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| pubmed:month |
Jun
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| pubmed:issn |
0028-1298
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| pubmed:author | |
| pubmed:issnType |
Print
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| pubmed:volume |
361
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| pubmed:owner |
NLM
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| pubmed:authorsComplete |
Y
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| pubmed:pagination |
636-45
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| pubmed:dateRevised |
2008-11-21
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| pubmed:meshHeading |
pubmed-meshheading:10882039-Animals,
pubmed-meshheading:10882039-Cells, Cultured,
pubmed-meshheading:10882039-Cycloheximide,
pubmed-meshheading:10882039-Cyclooxygenase 2,
pubmed-meshheading:10882039-DNA,
pubmed-meshheading:10882039-Dactinomycin,
pubmed-meshheading:10882039-Dexamethasone,
pubmed-meshheading:10882039-Enzyme Induction,
pubmed-meshheading:10882039-Gene Expression Regulation, Enzymologic,
pubmed-meshheading:10882039-Genes, Reporter,
pubmed-meshheading:10882039-I-kappa B Proteins,
pubmed-meshheading:10882039-Isoenzymes,
pubmed-meshheading:10882039-Kidney Glomerulus,
pubmed-meshheading:10882039-NF-kappa B,
pubmed-meshheading:10882039-Nucleic Acid Synthesis Inhibitors,
pubmed-meshheading:10882039-Platelet-Derived Growth Factor,
pubmed-meshheading:10882039-Prostaglandin-Endoperoxide Synthases,
pubmed-meshheading:10882039-Protein Synthesis Inhibitors,
pubmed-meshheading:10882039-RNA, Messenger,
pubmed-meshheading:10882039-Rats,
pubmed-meshheading:10882039-Transcriptional Activation
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| pubmed:year |
2000
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| pubmed:articleTitle |
Induction of cyclooxygenase-2 by platelet-derived growth factor (PDGF) and its inhibition by dexamethasone are independent of NF-kappaB/IkappaB transcription factors.
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| pubmed:affiliation |
Medizinische Klinik IV, Universität Erlangen-Nürnberg, Erlangen, Germany. Goppelt-Struebe@rzmail.uni-erlangen.de
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| pubmed:publicationType |
Journal Article,
Research Support, Non-U.S. Gov't
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