Dexamethasone destabilizes cyclooxygenase 2 mRNA by inhibiting mitogen-activated protein kinase p38.
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 mec...
| Main Authors: | , , , |
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| Format: | Journal article |
| Language: | English |
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2001
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| _version_ | 1826285266246041600 |
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| author | Lasa, M Brook, M Saklatvala, J Clark, A |
| author_facet | Lasa, M Brook, M Saklatvala, J Clark, A |
| author_sort | Lasa, M |
| collection | OXFORD |
| description | 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. |
| first_indexed | 2024-03-07T01:26:15Z |
| format | Journal article |
| id | oxford-uuid:921423e6-5a9d-493e-a257-7bbccbf5f35e |
| institution | University of Oxford |
| language | English |
| last_indexed | 2024-03-07T01:26:15Z |
| publishDate | 2001 |
| record_format | dspace |
| spelling | oxford-uuid:921423e6-5a9d-493e-a257-7bbccbf5f35e2022-03-26T23:23:02ZDexamethasone destabilizes cyclooxygenase 2 mRNA by inhibiting mitogen-activated protein kinase p38.Journal articlehttp://purl.org/coar/resource_type/c_dcae04bcuuid:921423e6-5a9d-493e-a257-7bbccbf5f35eEnglishSymplectic Elements at Oxford2001Lasa, MBrook, MSaklatvala, JClark, AThe 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. |
| spellingShingle | Lasa, M Brook, M Saklatvala, J Clark, A Dexamethasone destabilizes cyclooxygenase 2 mRNA by inhibiting mitogen-activated protein kinase p38. |
| title | Dexamethasone destabilizes cyclooxygenase 2 mRNA by inhibiting mitogen-activated protein kinase p38. |
| title_full | Dexamethasone destabilizes cyclooxygenase 2 mRNA by inhibiting mitogen-activated protein kinase p38. |
| title_fullStr | Dexamethasone destabilizes cyclooxygenase 2 mRNA by inhibiting mitogen-activated protein kinase p38. |
| title_full_unstemmed | Dexamethasone destabilizes cyclooxygenase 2 mRNA by inhibiting mitogen-activated protein kinase p38. |
| title_short | Dexamethasone destabilizes cyclooxygenase 2 mRNA by inhibiting mitogen-activated protein kinase p38. |
| title_sort | dexamethasone destabilizes cyclooxygenase 2 mrna by inhibiting mitogen activated protein kinase p38 |
| work_keys_str_mv | AT lasam dexamethasonedestabilizescyclooxygenase2mrnabyinhibitingmitogenactivatedproteinkinasep38 AT brookm dexamethasonedestabilizescyclooxygenase2mrnabyinhibitingmitogenactivatedproteinkinasep38 AT saklatvalaj dexamethasonedestabilizescyclooxygenase2mrnabyinhibitingmitogenactivatedproteinkinasep38 AT clarka dexamethasonedestabilizescyclooxygenase2mrnabyinhibitingmitogenactivatedproteinkinasep38 |