Abstract
The stability of cyclooxygenase 2 (Cox-2) mRNA is regulated positively by proinflammatory stimuli acting through mitogen-activated protein kinase (MAPK) p38 and negatively by anti-inflammatory glucocorticoids such as dexamethasone. A tetracycline-regulated reporter system was used to investigate mechanisms of regulation of Cox-2 mRNA stability. Dexamethasone was found to destabilize beta-globin-Cox-2 reporter mRNAs by inhibiting p38. This inhibition occurred at the level of p38 itself: stabilization of reporter mRNA by a kinase upstream of p38 was blocked by dexamethasone, while stabilization by a kinase downstream of p38 was insensitive to dexamethasone. Inhibition of p38 activity by dexamethasone was observed in a variety of cell types treated with different activating stimuli. Furthermore, inhibition of p38 was antagonized by the anti-glucocorticoid RU486 and was delayed and actinomycin D sensitive, suggesting that ongoing glucocorticoid receptor-dependent transcription is required.
Original language | English |
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Pages (from-to) | 771-80 |
Number of pages | 10 |
Journal | Molecular and Cellular Biology |
Volume | 21 |
Issue number | 3 |
DOIs | |
Publication status | Published - Feb 2001 |
Keywords
- 3' Untranslated Regions
- Anti-Inflammatory Agents
- Base Sequence
- Cyclooxygenase 2
- Dactinomycin
- Dexamethasone
- Enzyme Inhibitors
- Gene Expression
- Genes, Reporter
- Globins
- HeLa Cells
- Humans
- Isoenzymes
- Membrane Proteins
- Mifepristone
- Mitogen-Activated Protein Kinases
- Molecular Sequence Data
- Prostaglandin-Endoperoxide Synthases
- RNA Stability
- RNA, Messenger
- Tetracycline
- p38 Mitogen-Activated Protein Kinases