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Article: Differential effects of RU486 reveal distinct mechanisms for glucocorticoid repression of prostaglandin E2 release

TitleDifferential effects of RU486 reveal distinct mechanisms for glucocorticoid repression of prostaglandin E2 release
Authors
Issue Date2004
PublisherBlackwell Publishing Ltd. The Journal's web site is located at http://www.blackwellpublishing.com/journals/EJB
Citation
European Journal Of Biochemistry, 2004, v. 271 n. 20, p. 4042-4052 How to Cite?
AbstractIn A549 pulmonary cells, the dexamethasone- and budesonide-dependent repression of interleukin-1β-induced prostaglandin E2 release was mimicked by the steroid antagonist, RU486. Conversely, whereas dexamethasone and budesonide were highly effective inhibitors of interleukin-1β-induced cyclooxygenase (COX)/prostaglandin E synthase (PGES) activity and COX-2 expression, RU486 (< 1 μM) was a poor inhibitor, but was able to efficiently antagonize the effects of dexamethasone and budesonide. In addition, both dexamethasone and RU486 repressed [3H]arachidonate release, which is consistent with an effect at the level of phospholipase A2 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-κB-dependent transcription was maximally 30-40% and RU486 (< 1 μM) was without significant effect. Thus, two pharmacologically distinct mechanisms of glucocorticoid-dependent repression of prostaglandin E2 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-κB in the repression of COX-2 is indicated.
Persistent Identifierhttp://hdl.handle.net/10722/163281
ISSN
2006 Impact Factor: 3.579
ISI Accession Number ID
References

 

DC FieldValueLanguage
dc.contributor.authorChivers, JEen_US
dc.contributor.authorCambridge, LMen_US
dc.contributor.authorCatley, MCen_US
dc.contributor.authorMak, JCen_US
dc.contributor.authorDonnelly, LEen_US
dc.contributor.authorBarnes, PJen_US
dc.contributor.authorNewton, Ren_US
dc.date.accessioned2012-09-05T05:29:36Z-
dc.date.available2012-09-05T05:29:36Z-
dc.date.issued2004en_US
dc.identifier.citationEuropean Journal Of Biochemistry, 2004, v. 271 n. 20, p. 4042-4052en_US
dc.identifier.issn0014-2956en_US
dc.identifier.urihttp://hdl.handle.net/10722/163281-
dc.description.abstractIn A549 pulmonary cells, the dexamethasone- and budesonide-dependent repression of interleukin-1β-induced prostaglandin E2 release was mimicked by the steroid antagonist, RU486. Conversely, whereas dexamethasone and budesonide were highly effective inhibitors of interleukin-1β-induced cyclooxygenase (COX)/prostaglandin E synthase (PGES) activity and COX-2 expression, RU486 (< 1 μM) was a poor inhibitor, but was able to efficiently antagonize the effects of dexamethasone and budesonide. In addition, both dexamethasone and RU486 repressed [3H]arachidonate release, which is consistent with an effect at the level of phospholipase A2 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-κB-dependent transcription was maximally 30-40% and RU486 (< 1 μM) was without significant effect. Thus, two pharmacologically distinct mechanisms of glucocorticoid-dependent repression of prostaglandin E2 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-κB in the repression of COX-2 is indicated.en_US
dc.languageengen_US
dc.publisherBlackwell Publishing Ltd. The Journal's web site is located at http://www.blackwellpublishing.com/journals/EJBen_US
dc.relation.ispartofEuropean Journal of Biochemistryen_US
dc.subject.meshArachidonic Acid - Antagonists & Inhibitors - Secretionen_US
dc.subject.meshBinding, Competitiveen_US
dc.subject.meshBudesonide - Pharmacologyen_US
dc.subject.meshCell Line, Tumoren_US
dc.subject.meshCell Nucleus - Metabolism - Ultrastructureen_US
dc.subject.meshCyclooxygenase Inhibitors - Pharmacologyen_US
dc.subject.meshDexamethasone - Pharmacologyen_US
dc.subject.meshDinoprostone - Antagonists & Inhibitors - Secretionen_US
dc.subject.meshDose-Response Relationship, Drugen_US
dc.subject.meshGlucocorticoids - Genetics - Metabolismen_US
dc.subject.meshHumansen_US
dc.subject.meshInhibitory Concentration 50en_US
dc.subject.meshInterleukin-1 - Pharmacology - Physiologyen_US
dc.subject.meshLuciferases - Metabolismen_US
dc.subject.meshMifepristone - Pharmacologyen_US
dc.subject.meshNf-Kappa B - Metabolismen_US
dc.subject.meshProstaglandin-Endoperoxide Synthases - Drug Effects - Metabolismen_US
dc.subject.meshRadioligand Assayen_US
dc.subject.meshReceptors, Glucocorticoid - Drug Effects - Metabolismen_US
dc.subject.meshResponse Elements - Drug Effects - Physiologyen_US
dc.subject.meshTranscription, Genetic - Drug Effects - Physiologyen_US
dc.titleDifferential effects of RU486 reveal distinct mechanisms for glucocorticoid repression of prostaglandin E2 releaseen_US
dc.typeArticleen_US
dc.identifier.emailMak, JC:judymak@hku.hken_US
dc.identifier.authorityMak, JC=rp00352en_US
dc.description.naturelink_to_subscribed_fulltexten_US
dc.identifier.doi10.1111/j.1432-1033.2004.04342.xen_US
dc.identifier.pmid15479233-
dc.identifier.scopuseid_2-s2.0-7044241375en_US
dc.relation.referenceshttp://www.scopus.com/mlt/select.url?eid=2-s2.0-7044241375&selection=ref&src=s&origin=recordpageen_US
dc.identifier.volume271en_US
dc.identifier.issue20en_US
dc.identifier.spage4042en_US
dc.identifier.epage4052en_US
dc.identifier.isiWOS:000224347500008-
dc.publisher.placeUnited Kingdomen_US
dc.identifier.scopusauthoridChivers, JE=6603554380en_US
dc.identifier.scopusauthoridCambridge, LM=36795594200en_US
dc.identifier.scopusauthoridCatley, MC=6602158721en_US
dc.identifier.scopusauthoridMak, JC=7103323094en_US
dc.identifier.scopusauthoridDonnelly, LE=7102000743en_US
dc.identifier.scopusauthoridBarnes, PJ=36064679400en_US
dc.identifier.scopusauthoridNewton, R=7401831692en_US

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