Please use this identifier to cite or link to this item: https://hdl.handle.net/2440/98105
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dc.contributor.authorManetsch, M.-
dc.contributor.authorRahman, M.-
dc.contributor.authorPatel, B.-
dc.contributor.authorRamsay, E.-
dc.contributor.authorRumzhum, N.-
dc.contributor.authorAlkhouri, H.-
dc.contributor.authorGe, Q.-
dc.contributor.authorAmmit, A.-
dc.contributor.editorIto, K.-
dc.date.issued2013-
dc.identifier.citationPLoS One, 2013; 8(3):e59635-1-e59635-9-
dc.identifier.issn1932-6203-
dc.identifier.issn1932-6203-
dc.identifier.urihttp://hdl.handle.net/2440/98105-
dc.description.abstractMitogen-activated protein kinase phosphatase 1 (MKP-1) represses MAPK-driven signalling and plays an important anti-inflammatory role in asthma and airway remodelling. Although MKP-1 is corticosteroid-responsive and increased by cAMP-mediated signalling, the upregulation of this critical anti-inflammatory protein by long-acting β2-agonists and clinically-used corticosteroids has been incompletely examined to date. To address this, we investigated MKP-1 gene expression and protein upregulation induced by two long-acting β2-agonists (salmeterol and formoterol), alone or in combination with the corticosteroid fluticasone propionate (abbreviated as fluticasone) in primary human airway smooth muscle (ASM) cells in vitro. β2-agonists increased MKP-1 protein in a rapid but transient manner, while fluticasone induced sustained upregulation. Together, long-acting β2-agonists increased fluticasone-induced MKP-1 and modulated ASM synthetic function (measured by interleukin 6 (IL-6) and interleukin 8 (IL-8) secretion). As IL-6 expression (like MKP-1) is cAMP/adenylate cyclase-mediated, the long-acting β2-agonist formoterol increased IL-6 mRNA expression and secretion. Nevertheless, when added in combination with fluticasone, β2-agonists significantly repressed IL-6 secretion induced by tumour necrosis factor α (TNFα). Conversely, as IL-8 is not cAMP-responsive, β2-agonists significantly inhibited TNFα-induced IL-8 in combination with fluticasone, where fluticasone alone was without repressive effect. In summary, long-acting β2-agonists increase fluticasone-induced MKP-1 in ASM cells and repress synthetic function of this immunomodulatory airway cell type.-
dc.description.statementofresponsibilityMelanie Manetsch, Md. Mostafizur Rahman, Brijeshkumar S. Patel, Emma E. Ramsay, Nowshin N. Rumzhum, Hatem Alkhouri, Qi Ge, Alaina J. Ammit-
dc.language.isoen-
dc.publisherPublic Library of Science-
dc.rights© 2013 Manetsch et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.-
dc.source.urihttp://dx.doi.org/10.1371/journal.pone.0059635-
dc.subjectCells, Cultured-
dc.subjectMyocytes, Smooth Muscle-
dc.subjectHumans-
dc.subjectAndrostadienes-
dc.subjectBlotting, Western-
dc.subjectEnzyme-Linked Immunosorbent Assay-
dc.subjectDual Specificity Phosphatase 1-
dc.subjectAdrenergic beta-2 Receptor Agonists-
dc.subjectReal-Time Polymerase Chain Reaction-
dc.subjectFluticasone-
dc.titleLong-acting β2-agonists increase fluticasone propionate-induced mitogen-activated protein kinase phosphatase 1 (MKP-1) in airway smooth muscle cells-
dc.title.alternativeLong-acting beta2-agonists increase fluticasone propionate-induced mitogen-activated protein kinase phosphatase 1 (MKP-1) in airway smooth muscle cells-
dc.typeJournal article-
dc.identifier.doi10.1371/journal.pone.0059635-
dc.relation.granthttp://purl.org/au-research/grants/nhmrc/570856-
pubs.publication-statusPublished-
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