Dexamethasone Destabilizes Cyclooxygenase 2 mRNA by Inhibiting Mitogen-Activated Protein Kinase p38
Open Access
- 1 February 2001
- journal article
- Published by Taylor & Francis in Molecular and Cellular Biology
- Vol. 21 (3) , 771-780
- https://doi.org/10.1128/mcb.21.3.771-780.2001
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 β-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.Keywords
This publication has 72 references indexed in Scilit:
- Glucocorticoid-mediated Destabilization of Cyclin D3 mRNA Involves RNA-Protein Interactions in the 3′-Untranslated Region of the mRNAJournal of Biological Chemistry, 2000
- Hormone‐activated nuclear receptors inhibit the stimulation of the JNK and ERK signalling pathways in endothelial cellsFEBS Letters, 1999
- Interleukin-1β Regulation of Inducible Nitric Oxide Synthase and Cyclooxygenase-2 Involves the p42/44 and p38 MAPK Signaling Pathways in Cardiac MyocytesHypertension, 1999
- Interleukin-17-induced Gene Expression in Articular Chondrocytes Is Associated with Activation of Mitogen-activated Protein Kinases and NF-κBJournal of Biological Chemistry, 1998
- Dissociation of Basal Turnover and Cytokine-Induced Transcript Stabilization of the Human Cyclooxygenase-2 mRNA by Mutagenesis of the 3′-Untranslated RegionBiochemical and Biophysical Research Communications, 1998
- Cytokine induction of cytosolic phospholipase A2 and cyclooxygenase-2 mRNA is suppressed by glucocorticoids in human epithelial cellsLife Sciences, 1996
- A novel kinase cascade triggered by stress and heat shock that stimulates MAPKAP kinase-2 and phosphorylation of the small heat shock proteinsPublished by Elsevier ,1994
- Interleukin-1 activates a novel protein kinase cascade that results in the phosphorylation of hsp27Cell, 1994
- Transcriptional interference between c-Jun and the glucocorticoid receptor: Mutual inhibition of DNA binding due to direct protein-protein interactionCell, 1990
- A conserved AU sequence from the 3′ untranslated region of GM-CSF mRNA mediates selective mRNA degradationCell, 1986