Switch to
| Predicate | Object |
|---|---|
| rdf:type | |
| lifeskim:mentions |
umls-concept:C0011777,
umls-concept:C0012472,
umls-concept:C0030685,
umls-concept:C0035143,
umls-concept:C0040649,
umls-concept:C0071504,
umls-concept:C0387583,
umls-concept:C0391871,
umls-concept:C0441712,
umls-concept:C0680255,
umls-concept:C1283071,
umls-concept:C1314939,
umls-concept:C1517945,
umls-concept:C1709305,
umls-concept:C1963578
|
| pubmed:issue |
48
|
| pubmed:dateCreated |
1998-12-23
|
| pubmed:abstractText |
The two cyclooxygenase (COX) isoforms convert arachidonic acid to precursor prostaglandins (PGs). Up-regulation of COX-2 is responsible for increased PG production in inflammation and is antagonized by corticosteriods such as dexamethasone. In human pulmonary A549 cells, interleukin-1beta (IL-1beta) increases prostaglandin E2 (PGE2) synthesis via dexamethasone-sensitive induction of COX-2. Nuclear run-off assays showed that COX-2 transcription rate was repressed 25-40% by dexamethasone, while PGE2 release, COX activity, and COX-2 protein were totally repressed. At the mRNA level, complete repression of COX-2 was only observed at later (6 h) time points. Preinduced COX-2 mRNA was also potently repressed by dexamethasone, yet suppression of transcription by actinomycin D showed little effect. This dexamethasone-dependent repression involved a reduced COX-2 mRNA half-life, was blocked by actinomycin D or cycloheximide, and was antagonized by the steroid antagonist RU38486. Repression of IL-1beta-induced PGE2 release, COX activity, and COX-2 protein by actinomycin D was only effective within the first hour following IL-1beta treatment, while dexamethasone was effective when added up to 10 h later, suggesting a functional role for post-transcriptional mechanisms of repression. Following dexamethasone treatment, shortening of the average length of COX-2 mRNA poly(A) tails was observed. Finally, ligation of the COX-2 3'-UTR to a heterologous reporter failed to confer dexamethasone sensitivity. In conclusion, these data indicate a major role for post-transcriptional mechanisms in the dexamethasone-dependent repression of COX-2 that require de novo glucocorticoid receptor-dependent transcription and translation. This mechanism involves shortening of the COX-2 poly(A) tail and requires determinants other than just the 3'-UTR for specificity.
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| pubmed:grant | |
| pubmed:language |
eng
|
| pubmed:journal | |
| pubmed:citationSubset |
IM
|
| pubmed:chemical |
http://linkedlifedata.com/resource/pubmed/chemical/Cycloheximide,
http://linkedlifedata.com/resource/pubmed/chemical/Cyclooxygenase 2,
http://linkedlifedata.com/resource/pubmed/chemical/Dactinomycin,
http://linkedlifedata.com/resource/pubmed/chemical/Dexamethasone,
http://linkedlifedata.com/resource/pubmed/chemical/Dinoprostone,
http://linkedlifedata.com/resource/pubmed/chemical/Hormone Antagonists,
http://linkedlifedata.com/resource/pubmed/chemical/Interleukin-1,
http://linkedlifedata.com/resource/pubmed/chemical/Isoenzymes,
http://linkedlifedata.com/resource/pubmed/chemical/Membrane Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/Mifepristone,
http://linkedlifedata.com/resource/pubmed/chemical/PTGS2 protein, human,
http://linkedlifedata.com/resource/pubmed/chemical/Prostaglandin-Endoperoxide Synthases,
http://linkedlifedata.com/resource/pubmed/chemical/RNA, Messenger
|
| pubmed:status |
MEDLINE
|
| pubmed:month |
Nov
|
| pubmed:issn |
0021-9258
|
| pubmed:author | |
| pubmed:issnType |
Print
|
| pubmed:day |
27
|
| pubmed:volume |
273
|
| pubmed:owner |
NLM
|
| pubmed:authorsComplete |
Y
|
| pubmed:pagination |
32312-21
|
| pubmed:dateRevised |
2009-9-29
|
| pubmed:meshHeading |
pubmed-meshheading:9822711-Cycloheximide,
pubmed-meshheading:9822711-Cyclooxygenase 2,
pubmed-meshheading:9822711-Dactinomycin,
pubmed-meshheading:9822711-Dexamethasone,
pubmed-meshheading:9822711-Dinoprostone,
pubmed-meshheading:9822711-Enzyme Induction,
pubmed-meshheading:9822711-Hormone Antagonists,
pubmed-meshheading:9822711-Humans,
pubmed-meshheading:9822711-Interleukin-1,
pubmed-meshheading:9822711-Isoenzymes,
pubmed-meshheading:9822711-Kinetics,
pubmed-meshheading:9822711-Lung,
pubmed-meshheading:9822711-Lung Neoplasms,
pubmed-meshheading:9822711-Membrane Proteins,
pubmed-meshheading:9822711-Mifepristone,
pubmed-meshheading:9822711-Prostaglandin-Endoperoxide Synthases,
pubmed-meshheading:9822711-RNA, Messenger,
pubmed-meshheading:9822711-RNA Processing, Post-Transcriptional,
pubmed-meshheading:9822711-Repetitive Sequences, Nucleic Acid,
pubmed-meshheading:9822711-Transcription, Genetic,
pubmed-meshheading:9822711-Tumor Cells, Cultured
|
| pubmed:year |
1998
|
| pubmed:articleTitle |
Repression of cyclooxygenase-2 and prostaglandin E2 release by dexamethasone occurs by transcriptional and post-transcriptional mechanisms involving loss of polyadenylated mRNA.
|
| pubmed:affiliation |
Department of Thoracic Medicine, National Heart and Lung Institute, Imperial College School of Medicine, Dovehouse Street, London, SW3 6LY, United Kingdom. robert.newton@ic.ac.uk
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| pubmed:publicationType |
Journal Article,
Research Support, Non-U.S. Gov't
|