{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,4]],"date-time":"2026-10-04T20:52:42Z","timestamp":1791147162925,"version":"4.1.0"},"reference-count":48,"publisher":"Public Library of Science (PLoS)","issue":"2","license":[{"start":{"date-parts":[[2012,2,21]],"date-time":"2012-02-21T00:00:00Z","timestamp":1329782400000},"content-version":"unspecified","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["www.plosone.org"],"crossmark-restriction":false},"short-container-title":["PLoS ONE"],"DOI":"10.1371\/journal.pone.0031574","type":"journal-article","created":{"date-parts":[[2012,2,21]],"date-time":"2012-02-21T22:49:34Z","timestamp":1329864574000},"page":"e31574","update-policy":"https:\/\/doi.org\/10.1371\/journal.pone.corrections_policy","source":"Crossref","is-referenced-by-count":66,"title":["Anti-Inflammatory Role of the cAMP Effectors Epac and PKA: Implications in Chronic Obstructive Pulmonary Disease"],"prefix":"10.1371","volume":"7","author":[{"given":"Anouk","family":"Oldenburger","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sara S.","family":"Roscioni","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Esther","family":"Jansen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mark H.","family":"Menzen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andrew J.","family":"Halayko","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wim","family":"Timens","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Herman","family":"Meurs","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Harm","family":"Maarsingh","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Martina","family":"Schmidt","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"340","published-online":{"date-parts":[[2012,2,21]]},"reference":[{"key":"ref1","doi-asserted-by":"crossref","first-page":"435","DOI":"10.1146\/annurev.pathol.4.110807.092145","article-title":"The pathology of chronic obstructive pulmonary disease.","volume":"4","author":"JC Hogg","year":"2009","journal-title":"Annu Rev Pathol"},{"key":"ref2","doi-asserted-by":"crossref","first-page":"1065","DOI":"10.1016\/j.jaci.2006.12.640","article-title":"The neutrophil in chronic obstructive pulmonary disease.","volume":"119","author":"JK Quint","year":"2007","journal-title":"J Allergy Clin Immunol"},{"key":"ref3","doi-asserted-by":"crossref","first-page":"2329","DOI":"10.1016\/S0002-9440(10)63589-4","article-title":"Neutrophil elastase contributes to cigarette smoke-induced emphysema in mice.","volume":"163","author":"SD Shapiro","year":"2003","journal-title":"Am J Pathol"},{"key":"ref4","doi-asserted-by":"crossref","first-page":"267","DOI":"10.1136\/thx.51.3.267","article-title":"Airways obstruction, chronic expectoration, and rapid decline of FEV1 in smokers are associated with increased levels of sputum neutrophils.","volume":"51","author":"D Stanescu","year":"1996","journal-title":"Thorax"},{"key":"ref5","doi-asserted-by":"crossref","first-page":"71","DOI":"10.1164\/rccm.200505-704OC","article-title":"Systemic and upper and lower airway inflammation at exacerbation of chronic obstructive pulmonary disease.","volume":"173","author":"JR Hurst","year":"2006","journal-title":"Am J Respir Crit Care Med"},{"key":"ref6","doi-asserted-by":"crossref","first-page":"505","DOI":"10.1378\/chest.112.2.505","article-title":"Airway inflammation in COPD assessed by sputum levels of interleukin-8.","volume":"112","author":"C Yamamoto","year":"1997","journal-title":"Chest"},{"key":"ref7","doi-asserted-by":"crossref","first-page":"530","DOI":"10.1164\/ajrccm.153.2.8564092","article-title":"Differences in interleukin-8 and tumor necrosis factor-alpha in induced sputum from patients with chronic obstructive pulmonary disease or asthma.","volume":"153","author":"VM Keatings","year":"1996","journal-title":"Am J Respir Crit Care Med"},{"key":"ref8","doi-asserted-by":"crossref","first-page":"405","DOI":"10.1136\/thorax.57.5.405","article-title":"Increased levels of interleukin-8 in BAL fluid from smokers susceptible to pulmonary emphysema.","volume":"57","author":"M Tanino","year":"2002","journal-title":"Thorax"},{"key":"ref9","doi-asserted-by":"crossref","first-page":"1770","DOI":"10.1164\/ajrccm.155.5.9154890","article-title":"Cigarette smoke induces interleukin-8 release from human bronchial epithelial cells.","volume":"155","author":"T Mio","year":"1997","journal-title":"Am J Respir Crit Care Med"},{"key":"ref10","doi-asserted-by":"crossref","first-page":"1967","DOI":"10.1056\/NEJMoa041892","article-title":"Decreased histone deacetylase activity in chronic obstructive pulmonary disease.","volume":"352","author":"K Ito","year":"2005","journal-title":"N Engl J Med"},{"key":"ref11","doi-asserted-by":"crossref","first-page":"1045","DOI":"10.1007\/s00109-008-0360-0","article-title":"Salmeterol with fluticasone enhances the suppression of IL-8 release and increases the translocation of glucocorticoid receptor by human neutrophils stimulated with cigarette smoke.","volume":"86","author":"E Mortaz","year":"2008","journal-title":"J Mol Med"},{"key":"ref12","doi-asserted-by":"crossref","first-page":"L46","DOI":"10.1152\/ajplung.00241.2005","article-title":"Cigarette smoke induces proinflammatory cytokine release by activation of NF-kappaB and posttranslational modifications of histone deacetylase in macrophages.","volume":"291","author":"SR Yang","year":"2006","journal-title":"Am J Physiol Lung Cell Mol Physiol"},{"key":"ref13","doi-asserted-by":"crossref","first-page":"613","DOI":"10.1165\/rcmb.2003-0113OC","article-title":"Serine protease inhibitors modulate smoke-induced chemokine release from human lung fibroblasts.","volume":"29","author":"H Numanami","year":"2003","journal-title":"Am J Respir Cell Mol Biol"},{"key":"ref14","doi-asserted-by":"crossref","first-page":"130","DOI":"10.1186\/1465-9921-11-130","article-title":"Pro-inflammatory mechanisms of muscarinic receptor stimulation in airway smooth muscle.","volume":"11","author":"TA Oenema","year":"2010","journal-title":"Respir Res"},{"key":"ref15","doi-asserted-by":"crossref","first-page":"74","DOI":"10.1186\/1465-9921-6-74","article-title":"Cigarette smoke induces IL-8, but inhibits eotaxin and RANTES release from airway smooth muscle.","volume":"6","author":"U Oltmanns","year":"2005","journal-title":"Respir Res"},{"key":"ref16","doi-asserted-by":"crossref","first-page":"621","DOI":"10.1146\/annurev.immunol.18.1.621","article-title":"Phosphorylation meets ubiquitination: the control of NF-[kappa]B activity.","volume":"18","author":"M Karin","year":"2000","journal-title":"Annu Rev Immunol"},{"key":"ref17","doi-asserted-by":"crossref","first-page":"405","DOI":"10.1146\/annurev.cb.10.110194.002201","article-title":"Structure, regulation and function of NF-kappa B.","volume":"10","author":"U Siebenlist","year":"1994","journal-title":"Annu Rev Cell Biol"},{"key":"ref18","doi-asserted-by":"crossref","first-page":"73","DOI":"10.1097\/00029330-200801010-00014","article-title":"Role of the extracellular signal-regulated kinase 1\/2 signaling pathway in regulating the secretion of bronchial smooth muscle cells in a rat model of chronic asthma.","volume":"121","author":"M Xie","year":"2008","journal-title":"Chin Med J (Engl)"},{"key":"ref19","doi-asserted-by":"crossref","first-page":"1007","DOI":"10.1517\/14656566.1.5.1007","article-title":"Evaluation of current pharmacotherapy of chronic obstructive pulmonary disease.","volume":"1","author":"SV Culpitt","year":"2000","journal-title":"Expert Opin Pharmacother"},{"key":"ref20","doi-asserted-by":"crossref","first-page":"542","DOI":"10.1164\/ajrccm.155.2.9032192","article-title":"Effects of inhaled and oral glucocorticoids on inflammatory indices in asthma and COPD.","volume":"155","author":"VM Keatings","year":"1997","journal-title":"Am J Respir Crit Care Med"},{"key":"ref21","doi-asserted-by":"crossref","first-page":"736","DOI":"10.1164\/rccm.200508-1321OC","article-title":"Antiinflammatory effects of salmeterol\/fluticasone propionate in chronic obstructive lung disease.","volume":"173","author":"NC Barnes","year":"2006","journal-title":"Am J Respir Crit Care Med"},{"key":"ref22","doi-asserted-by":"crossref","first-page":"1038","DOI":"10.1016\/S0140-6736(11)61295-6","article-title":"Controversies in treatment of chronic obstructive pulmonary disease.","volume":"378","author":"KF Rabe","year":"2011","journal-title":"Lancet"},{"key":"ref23","doi-asserted-by":"crossref","first-page":"1286","DOI":"10.1183\/09031936.06.00112605","article-title":"Beyond the dogma: novel beta2-adrenoceptor signalling in the airways.","volume":"27","author":"MA Giembycz","year":"2006","journal-title":"Eur Respir J"},{"key":"ref24","first-page":"388","article-title":"Comparison of the effects of two long-acting beta2-agonists on cytokine secretion by human airway epithelial cells.","volume":"40","author":"JC Chiu","year":"2007","journal-title":"J Microbiol Immunol Infect"},{"key":"ref25","doi-asserted-by":"crossref","first-page":"729","DOI":"10.1038\/sj.bjp.0703866","article-title":"beta(2)-adrenoceptor agonists inhibit release of eosinophil-activating cytokines from human airway smooth muscle cells.","volume":"132","author":"MP Hallsworth","year":"2001","journal-title":"Br J Pharmacol"},{"key":"ref26","doi-asserted-by":"crossref","first-page":"L505","DOI":"10.1152\/ajplung.00046.2008","article-title":"Effect of beta2-adrenoceptor agonists and other cAMP-elevating agents on inflammatory gene expression in human ASM cells: a role for protein kinase A.","volume":"295","author":"M Kaur","year":"2008","journal-title":"Am J Physiol Lung Cell Mol Physiol"},{"key":"ref27","doi-asserted-by":"crossref","first-page":"446","DOI":"10.1016\/j.pupt.2008.10.006","article-title":"The effect of asthma therapeutics on signalling and transcriptional regulation of airway smooth muscle function.","volume":"22","author":"AJ Ammit","year":"2009","journal-title":"Pulm Pharmacol Ther"},{"key":"ref28","doi-asserted-by":"crossref","first-page":"179","DOI":"10.1016\/S1569-9048(03)00146-0","article-title":"Regulation of beta-adrenergic responses in airway smooth muscle.","volume":"137","author":"SA Shore","year":"2003","journal-title":"Respir Physiol Neurobiol"},{"key":"ref29","doi-asserted-by":"crossref","first-page":"80","DOI":"10.1513\/pats.200705-057VS","article-title":"Phenotype and functional plasticity of airway smooth muscle: role of caveolae and caveolins.","volume":"5","author":"AJ Halayko","year":"2008","journal-title":"Proc Am Thorac Soc"},{"key":"ref30","doi-asserted-by":"crossref","first-page":"277","DOI":"10.1016\/S1569-9048(03)00153-8","article-title":"Airway smooth muscle: immunomodulatory cells that modulate airway remodeling?","volume":"137","author":"RA Panettieri Jr","year":"2003","journal-title":"Respir Physiol Neurobiol"},{"key":"ref31","doi-asserted-by":"crossref","first-page":"88","DOI":"10.1186\/1465-9921-10-88","article-title":"PKA and Epac cooperate to augment bradykinin-induced interleukin-8 release from human airway smooth muscle cells.","volume":"10","author":"SS Roscioni","year":"2009","journal-title":"Respir Res"},{"key":"ref32","doi-asserted-by":"crossref","first-page":"2775","DOI":"10.1182\/blood-2004-03-1058","article-title":"Protein kinase A mediates inhibition of the thrombin-induced platelet shape change by nitric oxide.","volume":"104","author":"BO Jensen","year":"2004","journal-title":"Blood"},{"key":"ref33","doi-asserted-by":"crossref","first-page":"48","DOI":"10.1186\/1465-9921-11-48","article-title":"Cigarette smoke and lipopolysaccharide induce a proliferative airway smooth muscle phenotype.","volume":"11","author":"T Pera","year":"2010","journal-title":"Respir Res"},{"key":"ref34","doi-asserted-by":"crossref","first-page":"3546","DOI":"10.1172\/JCI36130","article-title":"The cytokine network in asthma and chronic obstructive pulmonary disease.","volume":"118","author":"PJ Barnes","year":"2008","journal-title":"J Clin Invest"},{"key":"ref35","doi-asserted-by":"crossref","first-page":"1666","DOI":"10.1164\/ajrccm.152.5.7582312","article-title":"Alveolar inflammation and its relation to emphysema in smokers.","volume":"152","author":"R Finkelstein","year":"1995","journal-title":"Am J Respir Crit Care Med"},{"key":"ref36","doi-asserted-by":"crossref","first-page":"532","DOI":"10.1164\/rccm.200703-456SO","article-title":"Global strategy for the diagnosis, management, and prevention of chronic obstructive pulmonary disease: GOLD executive summary.","volume":"176","author":"KF Rabe","year":"2007","journal-title":"Am J Respir Crit Care Med"},{"key":"ref37","doi-asserted-by":"crossref","first-page":"517","DOI":"10.7326\/0003-4819-151-8-200910200-00004","article-title":"Effect of fluticasone with and without salmeterol on pulmonary outcomes in chronic obstructive pulmonary disease: a randomized trial.","volume":"151","author":"TS Lapperre","year":"2009","journal-title":"Ann Intern Med"},{"key":"ref38","doi-asserted-by":"crossref","first-page":"292","DOI":"10.1016\/j.pupt.2007.07.001","article-title":"Fluticasone, but not salmeterol, reduces cigarette smoke-induced production of interleukin-8 in human airway smooth muscle.","volume":"21","author":"U Oltmanns","year":"2008","journal-title":"Pulm Pharmacol Ther"},{"key":"ref39","article-title":"Epac as a novel effector of airway smooth muscle relaxation.","author":"SS Roscioni","year":"2010","journal-title":"J Cell Mol Med"},{"key":"ref40","doi-asserted-by":"crossref","first-page":"193","DOI":"10.1111\/j.1476-5381.2010.01011.x","article-title":"cAMP inhibits modulation of airway smooth muscle phenotype via the exchange protein activated by cAMP (Epac) and protein kinase A.","volume":"162","author":"SS Roscioni","year":"2011","journal-title":"Br J Pharmacol"},{"key":"ref41","doi-asserted-by":"crossref","first-page":"370","DOI":"10.1016\/j.pupt.2007.10.004","article-title":"The pharmokinetic limitations of antioxidant treatment for COPD.","volume":"21","author":"R Foronjy","year":"2008","journal-title":"Pulm Pharmacol Ther"},{"key":"ref42","doi-asserted-by":"crossref","first-page":"6386","DOI":"10.1073\/pnas.0801490105","article-title":"The cyclic AMP effector Epac integrates pro- and anti-fibrotic signals.","volume":"105","author":"U Yokoyama","year":"2008","journal-title":"Proc Natl Acad Sci U S A"},{"key":"ref43","doi-asserted-by":"crossref","first-page":"S22","DOI":"10.1016\/S0954-6111(00)90129-X","article-title":"The effect of long-acting beta2-agonists on airway inflammation in asthmatic patients.","volume":"94","author":"PH Howarth","year":"2000","journal-title":"Respir Med"},{"key":"ref44","doi-asserted-by":"crossref","first-page":"275","DOI":"10.1034\/j.1399-3003.1999.14b07.x","article-title":"The long-acting beta2-agonist salmeterol xinafoate: effects on airway inflammation in asthma.","volume":"14","author":"JA Roberts","year":"1999","journal-title":"Eur Respir J"},{"key":"ref45","doi-asserted-by":"crossref","first-page":"2118","DOI":"10.1016\/S0140-6736(07)61906-0","article-title":"Effect of ADRB2 polymorphisms on response to longacting beta2-agonist therapy: a pharmacogenetic analysis of two randomised studies.","volume":"370","author":"ER Bleecker","year":"2007","journal-title":"Lancet"},{"key":"ref46","doi-asserted-by":"crossref","first-page":"151","DOI":"10.1016\/j.ejphar.2005.10.064","article-title":"Protein kinase C potentiates homologous desensitization of the beta2-adrenoceptor in bovine tracheal smooth muscle.","volume":"529","author":"M Boterman","year":"2006","journal-title":"Eur J Pharmacol"},{"key":"ref47","doi-asserted-by":"crossref","first-page":"440","DOI":"10.1165\/rcmb.2003-0241OC","article-title":"Extracellular matrix modulates beta2-adrenergic receptor signaling in human airway smooth muscle cells.","volume":"31","author":"AM Freyer","year":"2004","journal-title":"Am J Respir Cell Mol Biol"},{"key":"ref48","doi-asserted-by":"crossref","first-page":"L523","DOI":"10.1152\/ajplung.00013.2006","article-title":"Role of caveolin-1 in p42\/p44 MAP kinase activation and proliferation of human airway smooth muscle.","volume":"291","author":"R Gosens","year":"2006","journal-title":"Am J Physiol Lung Cell Mol Physiol"}],"container-title":["PLoS ONE"],"original-title":[],"language":"en","link":[{"URL":"http:\/\/dx.plos.org\/10.1371\/journal.pone.0031574","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2020,5,8]],"date-time":"2020-05-08T22:29:10Z","timestamp":1588976950000},"score":1,"resource":{"primary":{"URL":"https:\/\/dx.plos.org\/10.1371\/journal.pone.0031574"}},"subtitle":[],"editor":[{"given":"Oliver","family":"Eickelberg","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"editor"}]}],"short-title":[],"issued":{"date-parts":[[2012,2,21]]},"references-count":48,"journal-issue":{"issue":"2","published-online":{"date-parts":[[2012,2,21]]}},"URL":"https:\/\/doi.org\/10.1371\/journal.pone.0031574","relation":{},"ISSN":["1932-6203"],"issn-type":[{"value":"1932-6203","type":"electronic"}],"subject":[],"published":{"date-parts":[[2012,2,21]]}}}