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Differential effects of RU486 reveal distinct mechanisms for glucocorticoid repression of prostaglandin E-2 release
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UNSPECIFIED. (2004) Differential effects of RU486 reveal distinct mechanisms for glucocorticoid repression of prostaglandin E-2 release. EUROPEAN JOURNAL OF BIOCHEMISTRY, 271 (20). pp. 4042-4052. ISSN 0014-2956
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Official URL: http://dx.doi.org/10.1111/j.1432-1033.2004.04342.x
Abstract
In A549 pulmonary cells, the dexamethasone- and budesonide-dependent repression of interleukin-1beta-induced prostaglandin E-2 release was mimicked by the steroid antagonist, RU486. Conversely, whereas dexamethasone and budesonide were highly effective inhibitors of interleukin-1beta-induced cyclooxygenase (COX)/prostaglandin E synthase (PGES) activity and COX-2 expression, RU486 (< 1 mum) was a poor inhibitor, but was able to efficiently antagonize the effects of dexamethasone and budesonide. In addition, both dexamethasone and RU486 repressed [H-3]arachidonate release, which is consistent with an effect at the level of phospholipase A(2) activity. By contrast, glucocorticoid response element-dependent transcription was unaffected by RU486 but induced by dexamethasone and budesonide, whilst dexamethasone- and budesonide-dependent repression of nuclear factor-kappaB-dependent transcription was maximally 30-40% and RU486 (< 1 mum) was without significant effect. Thus, two pharmacologically distinct mechanisms of glucocorticoid-dependent repression of prostaglandin E-2 release are revealed. First, glucocorticoid-dependent repression of arachidonic acid is mimicked by RU486 and, second, repression of COX/PGES is antagonized by RU486. Finally, whilst all compounds induced glucocorticoid receptor translocation, no role for glucocorticoid response element-dependent transcription is supported in these inhibitory processes and only a limited role for glucocorticoid-dependent inhibition of nuclear factor-kappaB in the repression of COX-2 is indicated.
| Item Type: | Journal Article |
|---|---|
| Subjects: | Q Science > QD Chemistry |
| Journal or Publication Title: | EUROPEAN JOURNAL OF BIOCHEMISTRY |
| Publisher: | BLACKWELL PUBLISHING LTD |
| ISSN: | 0014-2956 |
| Date: | October 2004 |
| Volume: | 271 |
| Number: | 20 |
| Number of Pages: | 11 |
| Page Range: | pp. 4042-4052 |
| Identification Number: | 10.1111/j.1432-1033.2004.04342.x |
| Publication Status: | Published |
| URI: | http://wrap.warwick.ac.uk/id/eprint/7935 |
Data sourced from Thomson Reuters' Web of Knowledge
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