{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,30]],"date-time":"2026-04-30T03:57:55Z","timestamp":1777521475133,"version":"3.51.4"},"reference-count":51,"publisher":"Elsevier BV","license":[{"start":{"date-parts":[[2023,8,1]],"date-time":"2023-08-01T00:00:00Z","timestamp":1690848000000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.elsevier.com\/tdm\/userlicense\/1.0\/"},{"start":{"date-parts":[[2023,8,1]],"date-time":"2023-08-01T00:00:00Z","timestamp":1690848000000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.elsevier.com\/legal\/tdmrep-license"},{"start":{"date-parts":[[2023,8,1]],"date-time":"2023-08-01T00:00:00Z","timestamp":1690848000000},"content-version":"stm-asf","delay-in-days":0,"URL":"https:\/\/doi.org\/10.15223\/policy-017"},{"start":{"date-parts":[[2023,8,1]],"date-time":"2023-08-01T00:00:00Z","timestamp":1690848000000},"content-version":"stm-asf","delay-in-days":0,"URL":"https:\/\/doi.org\/10.15223\/policy-037"},{"start":{"date-parts":[[2023,8,1]],"date-time":"2023-08-01T00:00:00Z","timestamp":1690848000000},"content-version":"stm-asf","delay-in-days":0,"URL":"https:\/\/doi.org\/10.15223\/policy-012"},{"start":{"date-parts":[[2023,8,1]],"date-time":"2023-08-01T00:00:00Z","timestamp":1690848000000},"content-version":"stm-asf","delay-in-days":0,"URL":"https:\/\/doi.org\/10.15223\/policy-029"},{"start":{"date-parts":[[2023,8,1]],"date-time":"2023-08-01T00:00:00Z","timestamp":1690848000000},"content-version":"stm-asf","delay-in-days":0,"URL":"https:\/\/doi.org\/10.15223\/policy-004"}],"content-domain":{"domain":["elsevier.com","sciencedirect.com"],"crossmark-restriction":true},"short-container-title":["Molecular Immunology"],"published-print":{"date-parts":[[2023,8]]},"DOI":"10.1016\/j.molimm.2023.06.011","type":"journal-article","created":{"date-parts":[[2023,7,4]],"date-time":"2023-07-04T07:54:50Z","timestamp":1688457290000},"page":"95-102","update-policy":"https:\/\/doi.org\/10.1016\/elsevier_cm_policy","source":"Crossref","is-referenced-by-count":3,"special_numbering":"C","title":["Pro-inflammatory action of formoterol in human bronchial epithelia"],"prefix":"10.1016","volume":"160","author":[{"given":"Xing-Jian","family":"Liu","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Hao","family":"Pang","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yu-Qian","family":"Long","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ji-Qing","family":"Wang","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ya","family":"Niu","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Rui-Gang","family":"Zhang","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"78","reference":[{"key":"10.1016\/j.molimm.2023.06.011_bib1","doi-asserted-by":"crossref","first-page":"G753","DOI":"10.1152\/ajpgi.00130.2005","article-title":"A novel small molecule CFTR inhibitor attenuates HCO3- secretion and duodenal ulcer formation in rats","volume":"289","author":"Akiba","year":"2005","journal-title":"Am. J. Physiol. Gastrointest. Liver Physiol."},{"key":"10.1016\/j.molimm.2023.06.011_bib2","doi-asserted-by":"crossref","first-page":"119","DOI":"10.1385\/CRIAI:31:2:119","article-title":"Current issues with beta2-adrenoceptor agonists: pharmacology and molecular and cellular mechanisms","volume":"31","author":"Anderson","year":"2006","journal-title":"Clin. Rev. Allergy Immunol."},{"key":"10.1016\/j.molimm.2023.06.011_bib3","doi-asserted-by":"crossref","first-page":"19","DOI":"10.1016\/j.addr.2018.06.006","article-title":"Repurposing drugs as inhaled therapies in asthma","volume":"133","author":"Anderson","year":"2018","journal-title":"Adv. Drug Deliv. Rev."},{"key":"10.1016\/j.molimm.2023.06.011_bib4","doi-asserted-by":"crossref","first-page":"3577","DOI":"10.4049\/jimmunol.168.7.3577","article-title":"Activation of protease-activated receptor (PAR)-1, PAR-2, and PAR-4 stimulates IL-6, IL-8, and prostaglandin E2 release from human respiratory epithelial cells","volume":"168","author":"Asokananthan","year":"2002","journal-title":"J. Immunol."},{"key":"10.1016\/j.molimm.2023.06.011_bib5","doi-asserted-by":"crossref","first-page":"1160","DOI":"10.1038\/onc.2014.41","article-title":"PKA signaling drives mammary tumorigenesis through Src","volume":"34","author":"Beristain","year":"2015","journal-title":"Oncogene"},{"key":"10.1016\/j.molimm.2023.06.011_bib6","doi-asserted-by":"crossref","first-page":"329","DOI":"10.1007\/s00210-013-0950-4","article-title":"Non-raft adenylyl cyclase 2 defines a cAMP signaling compartment that selectively regulates IL-6 expression in airway smooth muscle cells: differential regulation of gene expression by AC isoforms","volume":"387","author":"Bogard","year":"2014","journal-title":"Naunyn Schmiede Arch. Pharmacol."},{"key":"10.1016\/j.molimm.2023.06.011_bib7","doi-asserted-by":"crossref","first-page":"135","DOI":"10.1042\/BJ20080029","article-title":"Evidence for direct CFTR inhibition by CFTR(inh)-172 based on Arg347 mutagenesis","volume":"413","author":"Caci","year":"2008","journal-title":"Biochem J."},{"key":"10.1016\/j.molimm.2023.06.011_bib8","doi-asserted-by":"crossref","first-page":"783","DOI":"10.1111\/j.1742-1241.2002.tb11376.x","article-title":"From adrenaline to formoterol: advances in beta-agonist therapy in the treatment of asthma","volume":"56","author":"Campbell","year":"2002","journal-title":"Int. J. Clin. Pract."},{"key":"10.1016\/j.molimm.2023.06.011_bib9","doi-asserted-by":"crossref","DOI":"10.1371\/journal.pone.0012091","article-title":"Polarized secretion of interleukin (IL)-6 and IL-8 by human airway epithelia 16HBE14o- cells in response to cationic polypeptide challenge","volume":"5","author":"Chow","year":"2010","journal-title":"PLoS One"},{"key":"10.1016\/j.molimm.2023.06.011_bib10","doi-asserted-by":"crossref","first-page":"521","DOI":"10.1111\/j.1476-5381.2011.01257.x","article-title":"Formoterol and salmeterol induce a similar degree of \u03b22-adrenoceptor tolerance in human small airways but via different mechanisms","volume":"163","author":"Cooper","year":"2011","journal-title":"Br. J. Pharmacol."},{"key":"10.1016\/j.molimm.2023.06.011_bib11","doi-asserted-by":"crossref","first-page":"38","DOI":"10.1165\/ajrcmb.10.1.7507342","article-title":"CFTR expression and chloride secretion in polarized immortal human bronchial epithelial cells","volume":"10","author":"Cozens","year":"1994","journal-title":"Am. J. Respir. Cell Mol. Biol."},{"key":"10.1016\/j.molimm.2023.06.011_bib12","doi-asserted-by":"crossref","DOI":"10.3389\/fphys.2021.690247","article-title":"Role of protein kinase A-mediated phosphorylation in CFTR channel activity regulation","volume":"12","author":"Della Sala","year":"2021","journal-title":"Front. Physiol."},{"key":"10.1016\/j.molimm.2023.06.011_bib13","doi-asserted-by":"crossref","first-page":"559","DOI":"10.1165\/rcmb.2013-0258OC","article-title":"Cigarette smoke activates the proto-oncogene c-src to promote airway inflammation and lung tissue destruction","volume":"50","author":"Geraghty","year":"2014","journal-title":"Am. J. Respir. Cell Mol. Biol."},{"key":"10.1016\/j.molimm.2023.06.011_bib14","doi-asserted-by":"crossref","first-page":"18440","DOI":"10.1074\/jbc.M200468200","article-title":"Protein kinase C and ERK activation are required for TFF-peptide-stimulated bronchial epithelial cell migration and tumor necrosis factor-alpha-induced interleukin-6 (IL-6) and IL-8 secretion","volume":"277","author":"Graness","year":"2002","journal-title":"J. Biol. Chem."},{"key":"10.1016\/j.molimm.2023.06.011_bib15","doi-asserted-by":"crossref","DOI":"10.1371\/journal.pone.0132835","article-title":"Cilostazol Induces PGI2 production via activation of the downstream Epac-1\/Rap1 signaling cascade to increase intracellular calcium by PLC\u03b5 and to activate p44\/42 MAPK in human aortic endothelial cells","volume":"10","author":"Hashimoto","year":"2015","journal-title":"PLoS One"},{"key":"10.1016\/j.molimm.2023.06.011_bib16","doi-asserted-by":"crossref","first-page":"3274","DOI":"10.1210\/en.2014-1247","article-title":"Activators of PKA and Epac distinctly influence insulin secretion and cytosolic Ca2+ in female mouse islets stimulated by glucose and tolbutamide","volume":"155","author":"Henquin","year":"2014","journal-title":"Endocrinology"},{"key":"10.1016\/j.molimm.2023.06.011_bib17","first-page":"27","article-title":"\u03b22-Adrenergic receptor signaling pathway stimulates the migration and invasion of cancer cells via Src activation","author":"Jeong","year":"2022","journal-title":"Molecules"},{"key":"10.1016\/j.molimm.2023.06.011_bib18","doi-asserted-by":"crossref","first-page":"S146","DOI":"10.1164\/ajrccm.158.supplement_2.13tac110","article-title":"The beta-adrenoceptor","volume":"158","author":"Johnson","year":"1998","journal-title":"Am. J. Respir. Crit. Care Med."},{"key":"10.1016\/j.molimm.2023.06.011_bib19","first-page":"21","article-title":"Airway inflammation and host responses in the Era of CFTR Modulators","author":"Keown","year":"2020","journal-title":"Int. J. Mol. Sci."},{"key":"10.1016\/j.molimm.2023.06.011_bib20","doi-asserted-by":"crossref","first-page":"L1028","DOI":"10.1152\/ajplung.00479.2005","article-title":"Zn2+-induced IL-8 expression involves AP-1, JNK, and ERK activities in human airway epithelial cells","volume":"290","author":"Kim","year":"2006","journal-title":"Am. J. Physiol. Lung Cell Mol. Physiol."},{"key":"10.1016\/j.molimm.2023.06.011_bib21","doi-asserted-by":"crossref","DOI":"10.1371\/journal.pone.0142212","article-title":"Long-acting beta agonists enhance allergic airway disease","volume":"10","author":"Knight","year":"2015","journal-title":"PLoS One"},{"key":"10.1016\/j.molimm.2023.06.011_bib22","doi-asserted-by":"crossref","DOI":"10.1016\/j.str.2020.01.001","article-title":"Biased signaling of the G-Protein-coupled receptor \u03b2(2)AR is governed by conformational exchange kinetics","volume":"28","author":"Lamichhane","year":"2020","journal-title":"Structure"},{"key":"10.1016\/j.molimm.2023.06.011_bib23","doi-asserted-by":"crossref","first-page":"2297","DOI":"10.1016\/j.cellsig.2012.07.010","article-title":"Clenbuterol upregulates histone demethylase JHDM2a via the \u03b22-adrenoceptor\/cAMP\/PKA\/p-CREB signaling pathway","volume":"24","author":"Li","year":"2012","journal-title":"Cell Signal"},{"key":"10.1016\/j.molimm.2023.06.011_bib24","doi-asserted-by":"crossref","first-page":"27","DOI":"10.1007\/978-3-642-54490-3_2","article-title":"Dasatinib","volume":"201","author":"Lindauer","year":"2014","journal-title":"Recent Results Cancer Res."},{"key":"10.1016\/j.molimm.2023.06.011_bib25","doi-asserted-by":"crossref","first-page":"29","DOI":"10.1007\/978-3-319-91439-8_2","article-title":"Dasatinib","volume":"212","author":"Lindauer","year":"2018","journal-title":"Recent Results Cancer Res"},{"key":"10.1016\/j.molimm.2023.06.011_bib26","doi-asserted-by":"crossref","first-page":"186","DOI":"10.1007\/s12031-010-9426-x","article-title":"Differential roles of PKA and Epac on the production of cytokines in the endotoxin-stimulated primary cultured microglia","volume":"45","author":"Liu","year":"2011","journal-title":"J. Mol. Neurosci."},{"key":"10.1016\/j.molimm.2023.06.011_bib27","doi-asserted-by":"crossref","first-page":"655","DOI":"10.1126\/science.283.5402.655","article-title":"Beta-arrestin-dependent formation of beta2 adrenergic receptor-Src protein kinase complexes","volume":"283","author":"Luttrell","year":"1999","journal-title":"Science"},{"key":"10.1016\/j.molimm.2023.06.011_bib28","doi-asserted-by":"crossref","first-page":"9572","DOI":"10.1074\/jbc.275.13.9572","article-title":"The beta(2)-adrenergic receptor mediates extracellular signal-regulated kinase activation via assembly of a multi-receptor complex with the epidermal growth factor receptor","volume":"275","author":"Maudsley","year":"2000","journal-title":"J. Biol. Chem."},{"key":"10.1016\/j.molimm.2023.06.011_bib29","doi-asserted-by":"crossref","first-page":"1106","DOI":"10.1242\/jcs.089086","article-title":"CFTR regulation in human airway epithelial cells requires integrity of the actin cytoskeleton and compartmentalized cAMP and PKA activity","volume":"125","author":"Monterisi","year":"2012","journal-title":"J. Cell Sci."},{"key":"10.1016\/j.molimm.2023.06.011_bib30","doi-asserted-by":"crossref","first-page":"E9163","DOI":"10.1073\/pnas.1710196114","article-title":"beta2-Adrenoceptor signaling in airway epithelial cells promotes eosinophilic inflammation, mucous metaplasia, and airway contractility","volume":"114","author":"Nguyen","year":"2017","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"10.1016\/j.molimm.2023.06.011_bib31","doi-asserted-by":"crossref","first-page":"5488","DOI":"10.1074\/jbc.M608495200","article-title":"Epac-mediated activation of phospholipase C(epsilon) plays a critical role in beta-adrenergic receptor-dependent enhancement of Ca2+ mobilization in cardiac myocytes","volume":"282","author":"Oestreich","year":"2007","journal-title":"J. Biol. Chem."},{"key":"10.1016\/j.molimm.2023.06.011_bib32","doi-asserted-by":"crossref","first-page":"42","DOI":"10.1016\/j.ejphar.2009.12.035","article-title":"beta2-Adrenoceptor, Gs and adenylate cyclase coupling in purified detergent-resistant, low density membrane fractions","volume":"630","author":"Oner","year":"2010","journal-title":"Eur. J. Pharmacol."},{"key":"10.1016\/j.molimm.2023.06.011_bib33","doi-asserted-by":"crossref","first-page":"256","DOI":"10.1124\/pr.116.013367","article-title":"The diverse roles of arrestin scaffolds in G protein-coupled receptor signaling","volume":"69","author":"Peterson","year":"2017","journal-title":"Pharmacol. Rev."},{"key":"10.1016\/j.molimm.2023.06.011_bib34","doi-asserted-by":"crossref","first-page":"L101","DOI":"10.1152\/ajplung.00125.2016","article-title":"\u03b22-Adrenergic agonists attenuate organic dust-induced lung inflammation","volume":"311","author":"Romberger","year":"2016","journal-title":"Am. J. Physiol. Lung Cell Mol. Physiol."},{"key":"10.1016\/j.molimm.2023.06.011_bib35","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":"Roscioni","year":"2009","journal-title":"Respir. Res."},{"key":"10.1016\/j.molimm.2023.06.011_bib36","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":"Roscioni","year":"2011","journal-title":"Br. J. Pharmacol."},{"key":"10.1016\/j.molimm.2023.06.011_bib37","doi-asserted-by":"crossref","first-page":"190","DOI":"10.1186\/s12974-019-1561-x","article-title":"Dasatinib regulates LPS-induced microglial and astrocytic neuroinflammatory responses by inhibiting AKT\/STAT3 signaling","volume":"16","author":"Ryu","year":"2019","journal-title":"J. Neuroinflamm."},{"key":"10.1016\/j.molimm.2023.06.011_bib38","doi-asserted-by":"crossref","first-page":"1261","DOI":"10.1074\/jbc.M506576200","article-title":"beta-arrestin-dependent, G protein-independent ERK1\/2 activation by the beta2 adrenergic receptor","volume":"281","author":"Shenoy","year":"2006","journal-title":"J. Biol. Chem."},{"key":"10.1016\/j.molimm.2023.06.011_bib39","doi-asserted-by":"crossref","first-page":"14","DOI":"10.1186\/1478-811X-9-14","article-title":"Src mediates cytokine-stimulated gene expression in airway myocytes through ERK MAPK","volume":"9","author":"Singer","year":"2011","journal-title":"Cell Commun. Signal"},{"key":"10.1016\/j.molimm.2023.06.011_bib40","doi-asserted-by":"crossref","first-page":"243","DOI":"10.1038\/nrd.2017.229","article-title":"Biased signalling: from simple switches to allosteric microprocessors","volume":"17","author":"Smith","year":"2018","journal-title":"Nat. Rev. Drug Discov."},{"key":"10.1016\/j.molimm.2023.06.011_bib41","first-page":"8530","article-title":"Norepinephrine inhibits the cytotoxicity of NK92\u2013MI cells via the \u03b22\u2013adrenoceptor\/cAMP\/PKA\/p\u2011CREB signaling pathway","volume":"17","author":"Sun","year":"2018","journal-title":"Mol. Med. Rep."},{"issue":"Suppl 1","key":"10.1016\/j.molimm.2023.06.011_bib42","first-page":"S167","article-title":"G-protein-coupled receptor phosphorylation: where, when and by whom","volume":"153","author":"Tobin","year":"2008","journal-title":"Br. J. Pharmacol."},{"key":"10.1016\/j.molimm.2023.06.011_bib43","doi-asserted-by":"crossref","first-page":"20577","DOI":"10.1074\/jbc.M513605200","article-title":"G-protein-coupled receptor kinase specificity for beta-arrestin recruitment to the beta2-adrenergic receptor revealed by fluorescence resonance energy transfer","volume":"281","author":"Violin","year":"2006","journal-title":"J. Biol. Chem."},{"key":"10.1016\/j.molimm.2023.06.011_bib44","doi-asserted-by":"crossref","first-page":"142","DOI":"10.1016\/j.coph.2014.03.007","article-title":"Role for \u03b2-arrestin in mediating paradoxical \u03b22AR and PAR2 signaling in asthma","volume":"16","author":"Walker","year":"2014","journal-title":"Curr. Opin. Pharm."},{"key":"10.1016\/j.molimm.2023.06.011_bib45","doi-asserted-by":"crossref","first-page":"573","DOI":"10.1093\/abbs\/gmx045","article-title":"Lithium and an EPAC-specific inhibitor ESI-09 synergistically suppress pancreatic cancer cell proliferation and survival","volume":"49","author":"Wang","year":"2017","journal-title":"Acta Biochim Biophys. Sin. (Shanghai)"},{"key":"10.1016\/j.molimm.2023.06.011_bib46","doi-asserted-by":"crossref","first-page":"1580","DOI":"10.1016\/j.cellsig.2016.05.006","article-title":"Phosphorylation of Src by phosphoinositide 3-kinase regulates beta-adrenergic receptor-mediated EGFR transactivation","volume":"28","author":"Watson","year":"2016","journal-title":"Cell Signal"},{"key":"10.1016\/j.molimm.2023.06.011_bib47","doi-asserted-by":"crossref","first-page":"L643","DOI":"10.1152\/ajplung.00373.2013","article-title":"cAMP-dependent protein kinase activation decreases cytokine release in bronchial epithelial cells","volume":"307","author":"Wyatt","year":"2014","journal-title":"Am. J. Physiol. Lung Cell Mol. Physiol."},{"key":"10.1016\/j.molimm.2023.06.011_bib48","doi-asserted-by":"crossref","first-page":"205","DOI":"10.1016\/j.molimm.2018.12.002","article-title":"Anti-inflammatory action of HO-1\/CO in human bronchial epithelium in response to cationic polypeptide challenge","volume":"105","author":"Zhang","year":"2019","journal-title":"Mol. Immunol."},{"key":"10.1016\/j.molimm.2023.06.011_bib49","doi-asserted-by":"crossref","first-page":"8387","DOI":"10.1002\/jcp.29683","article-title":"\u03b2(2) adrenoceptor signaling regulates ion transport in 16HBE14o- human airway epithelial cells","volume":"235","author":"Zhang","year":"2020","journal-title":"J. Cell Physiol."},{"key":"10.1016\/j.molimm.2023.06.011_bib50","doi-asserted-by":"crossref","first-page":"619","DOI":"10.1007\/s00408-021-00484-0","article-title":"\u03b2(2)-adrenoceptor activation stimulates IL-6 production via PKA, ERK1\/2, Src, and Beta-Arrestin2 signaling pathways in human bronchial epithelia","volume":"199","author":"Zhang","year":"2021","journal-title":"Lung"},{"key":"10.1016\/j.molimm.2023.06.011_bib51","doi-asserted-by":"crossref","first-page":"1149","DOI":"10.1038\/s41385-018-0013-8","article-title":"Increased intracellular Cl(-) concentration promotes ongoing inflammation in airway epithelium","volume":"11","author":"Zhang","year":"2018","journal-title":"Mucosal Immunol."}],"container-title":["Molecular Immunology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.elsevier.com\/content\/article\/PII:S0161589023001323?httpAccept=text\/xml","content-type":"text\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/api.elsevier.com\/content\/article\/PII:S0161589023001323?httpAccept=text\/plain","content-type":"text\/plain","content-version":"vor","intended-application":"text-mining"}],"deposited":{"date-parts":[[2025,9,27]],"date-time":"2025-09-27T13:46:44Z","timestamp":1758980804000},"score":1,"resource":{"primary":{"URL":"https:\/\/linkinghub.elsevier.com\/retrieve\/pii\/S0161589023001323"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2023,8]]},"references-count":51,"alternative-id":["S0161589023001323"],"URL":"https:\/\/doi.org\/10.1016\/j.molimm.2023.06.011","relation":{},"ISSN":["0161-5890"],"issn-type":[{"value":"0161-5890","type":"print"}],"subject":[],"published":{"date-parts":[[2023,8]]},"assertion":[{"value":"Elsevier","name":"publisher","label":"This article is maintained by"},{"value":"Pro-inflammatory action of formoterol in human bronchial epithelia","name":"articletitle","label":"Article Title"},{"value":"Molecular Immunology","name":"journaltitle","label":"Journal Title"},{"value":"https:\/\/doi.org\/10.1016\/j.molimm.2023.06.011","name":"articlelink","label":"CrossRef DOI link to publisher maintained version"},{"value":"article","name":"content_type","label":"Content Type"},{"value":"\u00a9 2023 Elsevier Ltd. All rights reserved.","name":"copyright","label":"Copyright"}]}}