The Effect of Phosphodiesterase Inhibitors on the Induction of Gene Expression by Long-Acting beta2-Adrenoceptor Agonists and Glucocorticoids

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atmire.migration.oldid1352
dc.contributor.advisorNewton, Robert
dc.contributor.advisorGiembycz, Mark
dc.contributor.authorBinMahfouz, Hawazen
dc.date.accessioned2013-09-13T20:47:12Z
dc.date.available2013-11-12T08:00:17Z
dc.date.issued2013-09-13
dc.date.submitted2013en
dc.description.abstractRecently, phosphodiesterases (PDE)4 inhibitors have received approval as a complementary anti-inflammatory treatment for chronic obstructive pulmonary disease (COPD) patients who are already taking long-acting β2-agonists (LABA)/inhaled corticosteroid (ICS) combination therapy. However, this benefit is seen only in patients of the severe, bronchitic, frequent exacerbator phenotype. Several strategies have been proposed to enhance the clinical efficacy of PDE4 inhibitors. One of these is the use of dual PDE3/4 inhibitors, which in addition to providing superior anti-inflammatory activity when compared to a PDE4 inhibitor alone, will also promote bronchodilatation. The present study demonstrates that a PDE3 plus a PDE4 inhibitor successfully sensitized BEAS-2B airway epithelial cells transfected with a cyclic adenosine 3',5'-monophosphate (cAMP)-response element luciferase reporter to the LABA, formoterol. Furthermore, PDE3 plus PDE4 inhibitors in combination prolonged and/or sensitized the ability of formoterol to induce several genes in BEAS-2B cells that have anti-inflammatory potential in the absence and presence of the glucocorticoid, dexamethasone. Collectively, these data suggest that LABA/ICS combination therapy in conjunction with an inhibitors of PDE3 and PDE4 may together improve clinical outcomes in larger a population of severe COPD patients.en_US
dc.identifier.citationBinMahfouz, H. (2013). The Effect of Phosphodiesterase Inhibitors on the Induction of Gene Expression by Long-Acting beta2-Adrenoceptor Agonists and Glucocorticoids (Master's thesis, University of Calgary, Calgary, Canada). Retrieved from https://prism.ucalgary.ca. doi:10.11575/PRISM/28088en_US
dc.identifier.doihttp://dx.doi.org/10.11575/PRISM/28088
dc.identifier.urihttp://hdl.handle.net/11023/964
dc.language.isoeng
dc.publisher.facultyGraduate Studies
dc.publisher.institutionUniversity of Calgaryen
dc.publisher.placeCalgaryen
dc.rightsUniversity of Calgary graduate students retain copyright ownership and moral rights for their thesis. You may use this material in any way that is permitted by the Copyright Act or through licensing that has been assigned to the document. For uses that are not allowable under copyright legislation or licensing, you are required to seek permission.
dc.subjectMolecular
dc.subjectMolecular
dc.subject.classificationPhosphodiesterase Inhibitorsen_US
dc.subject.classificationLong-Acting beta2-Adrenoceptoren_US
dc.subject.classificationGlucocorticoidsen_US
dc.subject.classificationAnti-inflammatory genesen_US
dc.subject.classificationchronic obstructive pulmonary diseaseen_US
dc.titleThe Effect of Phosphodiesterase Inhibitors on the Induction of Gene Expression by Long-Acting beta2-Adrenoceptor Agonists and Glucocorticoids
dc.typemaster thesis
thesis.degree.disciplineMedical Science
thesis.degree.grantorUniversity of Calgary
thesis.degree.nameMaster of Science (MSc)
ucalgary.item.requestcopytrue
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