{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,27]],"date-time":"2026-06-27T05:02:10Z","timestamp":1782536530312,"version":"3.54.5"},"reference-count":41,"publisher":"Elsevier BV","issue":"4","license":[{"start":{"date-parts":[[2013,4,1]],"date-time":"2013-04-01T00:00:00Z","timestamp":1364774400000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.elsevier.com\/tdm\/userlicense\/1.0\/"},{"start":{"date-parts":[[2013,4,1]],"date-time":"2013-04-01T00:00:00Z","timestamp":1364774400000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.elsevier.com\/legal\/tdmrep-license"}],"content-domain":{"domain":["molpharm.aspetjournals.org","elsevier.com","sciencedirect.com"],"crossmark-restriction":true},"short-container-title":["Molecular Pharmacology"],"published-print":{"date-parts":[[2013,4]]},"DOI":"10.1124\/mol.112.083493","type":"journal-article","created":{"date-parts":[[2013,2,7]],"date-time":"2013-02-07T06:57:26Z","timestamp":1360220246000},"page":"894-906","update-policy":"https:\/\/doi.org\/10.1016\/elsevier_cm_policy","source":"Crossref","is-referenced-by-count":39,"title":["Phosphodiesterase 4 Inhibitors Augment the Ability of Formoterol to Enhance Glucocorticoid-Dependent Gene Transcription in Human Airway Epithelial Cells: A Novel Mechanism for the Clinical Efficacy of Roflumilast in Severe Chronic Obstructive Pulmonary Disease"],"prefix":"10.1016","volume":"83","author":[{"given":"Thunicia","family":"Moodley","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sylvia M.","family":"Wilson","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Taruna","family":"Joshi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christopher F.","family":"Rider","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pawan","family":"Sharma","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dong","family":"Yan","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Robert","family":"Newton","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mark A.","family":"Giembycz","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"78","reference":[{"key":"10.1124\/mol.112.083493_bib1","doi-asserted-by":"crossref","first-page":"183","DOI":"10.1038\/nri2254","article-title":"Immunology of asthma and chronic obstructive pulmonary disease","volume":"8","author":"Barnes","year":"2008","journal-title":"Nat Rev Immunol"},{"key":"10.1124\/mol.112.083493_bib2","doi-asserted-by":"crossref","first-page":"26","DOI":"10.1177\/0091270006294529","article-title":"Dose-proportional intraindividual single- and repeated-dose pharmacokinetics of roflumilast, an oral, once-daily phosphodiesterase 4 inhibitor","volume":"47","author":"Bethke","year":"2007","journal-title":"J Clin Pharmacol"},{"key":"10.1124\/mol.112.083493_bib3","first-page":"375","article-title":"Does roflumilast decrease exacerbations in severe COPD patients not controlled by inhaled combination therapy? The REACT study protocol","volume":"7","author":"Calverley","year":"2012","journal-title":"Int J Chron Obstruct Pulmon Dis"},{"key":"10.1124\/mol.112.083493_bib4","doi-asserted-by":"crossref","first-page":"685","DOI":"10.1016\/S0140-6736(09)61255-1","article-title":"Roflumilast in symptomatic chronic obstructive pulmonary disease: two randomised clinical trials","volume":"374","author":"Calverley","year":"2009","journal-title":"Lancet"},{"key":"10.1124\/mol.112.083493_bib5","doi-asserted-by":"crossref","first-page":"48092","DOI":"10.1074\/jbc.M309421200","article-title":"p57KIP2 modulates stress-activated signaling by inhibiting c-Jun NH2-terminal kinase\/stress-activated protein Kinase","volume":"278","author":"Chang","year":"2003","journal-title":"J Biol Chem"},{"key":"10.1124\/mol.112.083493_bib6","doi-asserted-by":"crossref","first-page":"79","DOI":"10.1016\/j.mce.2007.04.013","article-title":"Anti-inflammatory functions of glucocorticoid-induced genes","volume":"275","author":"Clark","year":"2007","journal-title":"Mol Cell Endocrinol"},{"key":"10.1124\/mol.112.083493_bib7","doi-asserted-by":"crossref","first-page":"54","DOI":"10.1016\/j.pharmthera.2011.12.004","article-title":"Maps and legends: the quest for dissociated ligands of the glucocorticoid receptor","volume":"134","author":"Clark","year":"2012","journal-title":"Pharmacol Ther"},{"key":"10.1124\/mol.112.083493_bib8","doi-asserted-by":"crossref","first-page":"47","DOI":"10.1006\/pupt.1998.0115","article-title":"Cyclic nucleotide phosphodiesterase in human bronchial epithelial cells: characterization of isoenzymes and functional effects of PDE inhibitors","volume":"11","author":"Dent","year":"1998","journal-title":"Pulm Pharmacol Ther"},{"key":"10.1124\/mol.112.083493_bib9","doi-asserted-by":"crossref","first-page":"115","DOI":"10.1016\/j.jaci.2006.08.027","article-title":"The anti-inflammatory effect of glucocorticoids is mediated by glucocorticoid-induced leucine zipper in epithelial cells","volume":"119","author":"Eddleston","year":"2007","journal-title":"J Allergy Clin Immunol"},{"key":"10.1124\/mol.112.083493_bib10","doi-asserted-by":"crossref","first-page":"292","DOI":"10.1165\/ajrcmb.20.2.3140","article-title":"Identification and function of cyclic nucleotide phosphodiesterase isoenzymes in airway epithelial cells","volume":"20","author":"Fuhrmann","year":"1999","journal-title":"Am J Respir Cell Mol Biol"},{"key":"10.1124\/mol.112.083493_bib11","doi-asserted-by":"crossref","first-page":"979","DOI":"10.1002\/iub.245","article-title":"Emerging roles of glucocorticoid receptor phosphorylation in modulating glucocorticoid hormone action in health and disease","volume":"61","author":"Galliher-Beckley","year":"2009","journal-title":"IUBMB Life"},{"key":"10.1124\/mol.112.083493_bib12","first-page":"147","article-title":"Roflumilast: first phosphodiesterase 4 inhibitor approved for treatment of COPD","volume":"4","author":"Giembycz","year":"2010","journal-title":"Drug Des Devel Ther"},{"key":"10.1124\/mol.112.083493_bib13","doi-asserted-by":"crossref","first-page":"1090","DOI":"10.1038\/sj.bjp.0707627","article-title":"A Holy Grail of asthma management: toward understanding how long-acting \u03b2(2)-adrenoceptor agonists enhance the clinical efficacy of inhaled corticosteroids","volume":"153","author":"Giembycz","year":"2008","journal-title":"Br J Pharmacol"},{"key":"10.1124\/mol.112.083493_bib14","doi-asserted-by":"crossref","first-page":"415","DOI":"10.1007\/978-3-642-17969-3_18","article-title":"Harnessing the clinical efficacy of phosphodiesterase 4 inhibitors in inflammatory lung diseases: dual-selective phosphodiesterase inhibitors and novel combination therapies","volume":"204","author":"Giembycz","year":"2011","journal-title":"Handb Exp Pharmacol"},{"key":"10.1124\/mol.112.083493_bib15","doi-asserted-by":"crossref","first-page":"141","DOI":"10.3109\/15412551003758304","article-title":"Treatment of chronic obstructive pulmonary disease with roflumilast, a new phosphodiesterase 4 inhibitor","volume":"7","author":"Gross","year":"2010","journal-title":"COPD"},{"key":"10.1124\/mol.112.083493_bib16","doi-asserted-by":"crossref","first-page":"235","DOI":"10.1016\/j.pupt.2010.03.011","article-title":"The preclinical pharmacology of roflumilast\u2014a selective, oral phosphodiesterase 4 inhibitor in development for chronic obstructive pulmonary disease","volume":"23","author":"Hatzelmann","year":"2010","journal-title":"Pulm Pharmacol Ther"},{"key":"10.1124\/mol.112.083493_bib17","doi-asserted-by":"crossref","first-page":"21978","DOI":"10.1073\/pnas.0911684106","article-title":"Elevated cyclic AMP and PDE4 inhibition induce chemokine expression in human monocyte-derived macrophages","volume":"106","author":"Hertz","year":"2009","journal-title":"Proc Natl Acad Sci USA"},{"key":"10.1124\/mol.112.083493_bib18","doi-asserted-by":"crossref","first-page":"709","DOI":"10.1016\/S0140-6736(04)16900-6","article-title":"Pathophysiology of airflow limitation in chronic obstructive pulmonary disease","volume":"364","author":"Hogg","year":"2004","journal-title":"Lancet"},{"key":"10.1124\/mol.112.083493_bib19","doi-asserted-by":"crossref","first-page":"2645","DOI":"10.1056\/NEJMoa032158","article-title":"The nature of small-airway obstruction in chronic obstructive pulmonary disease","volume":"350","author":"Hogg","year":"2004","journal-title":"N Engl J Med"},{"key":"10.1124\/mol.112.083493_bib20","doi-asserted-by":"crossref","first-page":"19713","DOI":"10.1073\/pnas.1110226108","article-title":"\u03b22-Adrenoceptor agonist-induced RGS2 expression is a genomic mechanism of bronchoprotection that is enhanced by glucocorticoids","volume":"108","author":"Holden","year":"2011","journal-title":"Proc Natl Acad Sci USA"},{"key":"10.1124\/mol.112.083493_bib21","doi-asserted-by":"crossref","first-page":"410","DOI":"10.1111\/j.1476-5381.2010.00708.x","article-title":"Enhancement of inflammatory mediator release by \u03b22-adrenoceptor agonists in airway epithelial cells is reversed by glucocorticoid action","volume":"160","author":"Holden","year":"2010","journal-title":"Br J Pharmacol"},{"key":"10.1124\/mol.112.083493_bib22","doi-asserted-by":"crossref","first-page":"203","DOI":"10.1124\/mol.107.040121","article-title":"Long-acting beta2-adrenoceptor agonists synergistically enhance glucocorticoid-dependent transcription in human airway epithelial and smooth muscle cells","volume":"73","author":"Kaur","year":"2008","journal-title":"Mol Pharmacol"},{"key":"10.1124\/mol.112.083493_bib23","doi-asserted-by":"crossref","first-page":"1737","DOI":"10.1111\/j.1476-5381.2011.01620.x","article-title":"Corticosteroid-induced gene expression in allergen-challenged asthmatic subjects taking inhaled budesonide","volume":"165","author":"Kelly","year":"2012","journal-title":"Br J Pharmacol"},{"key":"10.1124\/mol.112.083493_bib24","doi-asserted-by":"crossref","first-page":"44","DOI":"10.1165\/ajrcmb.24.1.4027","article-title":"Effects of prostaglandin E2 and cAMP elevating drugs on GM-CSF release by cultured human airway smooth muscle cells. Relevance to asthma therapy","volume":"24","author":"Lazzeri","year":"2001","journal-title":"Am J Respir Cell Mol Biol"},{"key":"10.1124\/mol.112.083493_bib25","doi-asserted-by":"crossref","first-page":"928","DOI":"10.1164\/rccm.200910-1506OC","article-title":"Extracellular adenosine triphosphate and chronic obstructive pulmonary disease","volume":"181","author":"Lommatzsch","year":"2010","journal-title":"Am J Respir Crit Care Med"},{"key":"10.1124\/mol.112.083493_bib26","doi-asserted-by":"crossref","first-page":"833","DOI":"10.1124\/jpet.103.060020","article-title":"Adenovirus-mediated delivery and expression of a cAMP-dependent protein kinase inhibitor gene to BEAS-2B epithelial cells abolishes the anti-inflammatory effects of rolipram, salbutamol, and prostaglandin E2: a comparison with H-89","volume":"309","author":"Meja","year":"2004","journal-title":"J Pharmacol Exp Ther"},{"key":"10.1124\/mol.112.083493_bib27","doi-asserted-by":"crossref","first-page":"939","DOI":"10.1016\/S0893-133X(02)00381-0","article-title":"The phosphodiesterase type 4 inhibitor, rolipram, enhances glucocorticoid receptor function","volume":"27","author":"Miller","year":"2002","journal-title":"Neuropsychopharmacology"},{"key":"10.1124\/mol.112.083493_bib28","doi-asserted-by":"crossref","first-page":"3","DOI":"10.1186\/1475-2867-7-3","article-title":"Pathway interactions between MAPKs, mTOR, PKA, and the glucocorticoid receptor in lymphoid cells","volume":"7","author":"Miller","year":"2007","journal-title":"Cancer Cell Int"},{"key":"10.1124\/mol.112.083493_bib29","doi-asserted-by":"crossref","first-page":"29603","DOI":"10.1074\/jbc.M101522200","article-title":"Inhibition of AP-1 by the glucocorticoid-inducible protein GILZ","volume":"276","author":"Mittelstadt","year":"2001","journal-title":"J Biol Chem"},{"key":"10.1124\/mol.112.083493_bib30","doi-asserted-by":"crossref","first-page":"585","DOI":"10.1136\/thorax.58.7.585","article-title":"Exhaled leukotrienes and prostaglandins in COPD","volume":"58","author":"Montuschi","year":"2003","journal-title":"Thorax"},{"key":"10.1124\/mol.112.083493_bib31","doi-asserted-by":"crossref","first-page":"22933","DOI":"10.1016\/S0021-9258(18)41616-X","article-title":"Modulation of cell signaling pathways can enhance or impair glucocorticoid-induced gene expression without altering the state of receptor phosphorylation","volume":"268","author":"Moyer","year":"1993","journal-title":"J Biol Chem"},{"key":"10.1124\/mol.112.083493_bib32","doi-asserted-by":"crossref","first-page":"286","DOI":"10.1016\/j.pharmthera.2009.11.003","article-title":"Pharmacological strategies for improving the efficacy and therapeutic ratio of glucocorticoids in inflammatory lung diseases","volume":"125","author":"Newton","year":"2010","journal-title":"Pharmacol Ther"},{"key":"10.1124\/mol.112.083493_bib33","doi-asserted-by":"crossref","first-page":"527","DOI":"10.1183\/09031936.00092506","article-title":"Inflammatory changes, recovery and recurrence at COPD exacerbation","volume":"29","author":"Perera","year":"2007","journal-title":"Eur Respir J"},{"key":"10.1124\/mol.112.083493_bib34","doi-asserted-by":"crossref","first-page":"18","DOI":"10.1186\/1465-9921-12-18","article-title":"Reduction of exacerbations by the PDE4 inhibitor roflumilast\u2014the importance of defining different subsets of patients with COPD","volume":"12","author":"Rennard","year":"2011","journal-title":"Respir Res"},{"key":"10.1124\/mol.112.083493_bib35","doi-asserted-by":"crossref","first-page":"1811","DOI":"10.1210\/mend.13.11.0379","article-title":"p57Kip2, a glucocorticoid-induced inhibitor of cell cycle progression in HeLa cells","volume":"13","author":"Samuelsson","year":"1999","journal-title":"Mol Endocrinol"},{"key":"10.1124\/mol.112.083493_bib36","doi-asserted-by":"crossref","first-page":"L279","DOI":"10.1152\/ajplung.00170.2002","article-title":"Ubiquitous expression of phosphodiesterase 7A in human proinflammatory and immune cells","volume":"284","author":"Smith","year":"2003","journal-title":"Am J Physiol Lung Cell Mol Physiol"},{"key":"10.1124\/mol.112.083493_bib37","doi-asserted-by":"crossref","first-page":"1679","DOI":"10.1124\/mol.104.002246","article-title":"Discovery of BRL 50481 [3-(N,N-dimethylsulfonamido)-4-methyl-nitrobenzene], a selective inhibitor of phosphodiesterase 7: in vitro studies in human monocytes, lung macrophages, and CD8+ T-lymphocytes","volume":"66","author":"Smith","year":"2004","journal-title":"Mol Pharmacol"},{"key":"10.1124\/mol.112.083493_bib38","doi-asserted-by":"crossref","first-page":"1074","DOI":"10.1038\/ni.1637","article-title":"A critical function for CD200 in lung immune homeostasis and the severity of influenza infection","volume":"9","author":"Snelgrove","year":"2008","journal-title":"Nat Immunol"},{"key":"10.1124\/mol.112.083493_bib39","doi-asserted-by":"crossref","first-page":"224","DOI":"10.1016\/j.cell.2011.03.027","article-title":"Widespread negative response elements mediate direct repression by agonist-liganded glucocorticoid receptor","volume":"145","author":"Surjit","year":"2011","journal-title":"Cell"},{"key":"10.1124\/mol.112.083493_bib40","doi-asserted-by":"crossref","first-page":"6646","DOI":"10.4049\/jimmunol.0802348","article-title":"The novel lipopolysaccharide-binding protein CRISPLD2 is a critical serum protein to regulate endotoxin function","volume":"183","author":"Wang","year":"2009","journal-title":"J Immunol"},{"key":"10.1124\/mol.112.083493_bib41","doi-asserted-by":"crossref","first-page":"6788","DOI":"10.4049\/jimmunol.0902738","article-title":"Selective prostacyclin receptor agonism augments glucocorticoid-induced gene expression in human bronchial epithelial cells","volume":"183","author":"Wilson","year":"2009","journal-title":"J Immunol"}],"container-title":["Molecular Pharmacology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.elsevier.com\/content\/article\/PII:S0026895X24036927?httpAccept=text\/xml","content-type":"text\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/api.elsevier.com\/content\/article\/PII:S0026895X24036927?httpAccept=text\/plain","content-type":"text\/plain","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/syndication.highwire.org\/content\/doi\/10.1124\/mol.112.083493","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,2,19]],"date-time":"2025-02-19T11:05:31Z","timestamp":1739963131000},"score":1,"resource":{"primary":{"URL":"https:\/\/linkinghub.elsevier.com\/retrieve\/pii\/S0026895X24036927"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2013,4]]},"references-count":41,"journal-issue":{"issue":"4","published-print":{"date-parts":[[2013,4]]}},"alternative-id":["S0026895X24036927"],"URL":"https:\/\/doi.org\/10.1124\/mol.112.083493","relation":{},"ISSN":["0026-895X"],"issn-type":[{"value":"0026-895X","type":"print"}],"subject":[],"published":{"date-parts":[[2013,4]]},"assertion":[{"value":"Elsevier","name":"publisher","label":"This article is maintained by"},{"value":"Phosphodiesterase 4 Inhibitors Augment the Ability of Formoterol to Enhance Glucocorticoid-Dependent Gene Transcription in Human Airway Epithelial Cells: A Novel Mechanism for the Clinical Efficacy of Roflumilast in Severe Chronic Obstructive Pulmonary Disease","name":"articletitle","label":"Article Title"},{"value":"Molecular Pharmacology","name":"journaltitle","label":"Journal Title"},{"value":"https:\/\/doi.org\/10.1124\/mol.112.083493","name":"articlelink","label":"CrossRef DOI link to publisher maintained version"},{"value":"article","name":"content_type","label":"Content Type"},{"value":"\u00a9 2013 by The American Society for Pharmacology and Experimental Therapeutics","name":"copyright","label":"Copyright"}]}}