Differential effects of RU486 reveal distinct mechanisms for glucocorticoid repression of prostaglandin E-2 release
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 0014-2956Full text not available from this repository.
Official URL: http://dx.doi.org/10.1111/j.1432-1033.2004.04342.x
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|
|Number of Pages:||11|
|Page Range:||pp. 4042-4052|
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