{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,6]],"date-time":"2026-10-06T01:02:04Z","timestamp":1791248524803,"version":"4.1.0"},"reference-count":46,"publisher":"Oxford University Press (OUP)","issue":"3","license":[{"start":{"date-parts":[[2010,8,1]],"date-time":"2010-08-01T00:00:00Z","timestamp":1280620800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/pages\/standard-publication-reuse-rights"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2010,8,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Rationale<\/jats:title>\n                    <jats:p>Airway inflammation is a central feature of chronic obstructive pulmonary disease (COPD). COPD exacerbations are often triggered by rhinovirus (RV) infection.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Objectives<\/jats:title>\n                    <jats:p>We hypothesized that airway epithelial cells from patients with COPD maintain a proinflammatory phenotype compared with control subjects, leading to greater RV responses.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>Cells were isolated from tracheobronchial tissues of 12 patients with COPD and 10 transplant donors. Eight patients with COPD had severe emphysema, three had mild to moderate emphysema, and one had no emphysema. All had moderate to severe airflow obstruction, and six met criteria for chronic bronchitis or had at least one exacerbation the previous year. Cells were grown at air\u2013liquid interface and infected with RV serotype 39. Cytokine and IFN expression was measured by ELISA. Selected genes involved in inflammation, oxidative stress, and proteolysis were assessed by focused gene array and real-time polymerase chain reaction.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Measurements and Main Results<\/jats:title>\n                    <jats:p>Compared with control subjects, cells from patients with COPD demonstrated increased mRNA expression of genes involved in oxidative stress and the response to viral infection, including NOX1, DUOXA2, MMP12, ICAM1, DDX58\/RIG-I, STAT1, and STAT2. COPD cells showed elevated baseline and RV-stimulated protein levels of IL-6, IL-8\/CXCL8, and growth-related oncogene-\u03b1\/CXCL1. COPD cells demonstrated increased viral titer and copy number after RV infection, despite increased IL-29\/IFN-\u03bb1, IL-28A\/IFN-\u03bb2, and IFN-inducible protein-10\/CXCL10 protein levels. Finally, RV-infected COPD cultures showed increased mRNA expression of IL28A\/IFN\u03bb2, IL29\/IFN\u03bb1, IFIH1\/MDA5, DDX58\/RIG-I, DUOX1, DUOX2, IRF7, STAT1, and STAT2.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>Airway epithelial cells from patients with COPD show higher baseline levels of cytokine expression and increased susceptibility to RV infection, despite an increased IFN response.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1164\/rccm.200911-1673oc","type":"journal-article","created":{"date-parts":[[2010,4,15]],"date-time":"2010-04-15T22:40:05Z","timestamp":1271371205000},"page":"332-340","source":"Crossref","is-referenced-by-count":160,"title":["Increased Cytokine Response of Rhinovirus-infected Airway Epithelial Cells in Chronic Obstructive Pulmonary Disease"],"prefix":"10.1093","volume":"182","author":[{"given":"Dina","family":"Schneider","sequence":"first","affiliation":[{"name":"Departments of Pediatrics and Communicable Diseases"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shyamala","family":"Ganesan","sequence":"additional","affiliation":[{"name":"Departments of Pediatrics and Communicable Diseases"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Adam T.","family":"Comstock","sequence":"additional","affiliation":[{"name":"Departments of Pediatrics and Communicable Diseases"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Catherine A.","family":"Meldrum","sequence":"additional","affiliation":[{"name":"Internal Medicine, University of Michigan, Ann Arbor, Michigan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Raja","family":"Mahidhara","sequence":"additional","affiliation":[{"name":"Internal Medicine, University of Michigan, Ann Arbor, Michigan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Adam M.","family":"Goldsmith","sequence":"additional","affiliation":[{"name":"Departments of Pediatrics and Communicable Diseases"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jeffrey L.","family":"Curtis","sequence":"additional","affiliation":[{"name":"Internal Medicine, University of Michigan, Ann Arbor, Michigan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fernando J.","family":"Martinez","sequence":"additional","affiliation":[{"name":"Internal Medicine, University of Michigan, Ann Arbor, Michigan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marc B.","family":"Hershenson","sequence":"additional","affiliation":[{"name":"Departments of Pediatrics and Communicable Diseases"},{"name":"Molecular and Integrative Physiology, and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Umadevi","family":"Sajjan","sequence":"additional","affiliation":[{"name":"Departments of Pediatrics and Communicable Diseases"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2010,8,1]]},"reference":[{"key":"2026032101493543500_BIB1","first-page":"114","volume-title":"Thorax","year":"2000"},{"key":"2026032101493543500_BIB2","first-page":"1112","volume-title":"Eur Respir J","year":"2001"},{"key":"2026032101493543500_BIB3","first-page":"349","volume-title":"Am J Respir Crit Care Med","year":"2001"},{"key":"2026032101493543500_BIB4","first-page":"1618","volume-title":"Am J Respir Crit Care Med","year":"2001"},{"key":"2026032101493543500_BIB5","first-page":"968","volume-title":"Am J Respir Crit Care Med","year":"2003"},{"key":"2026032101493543500_BIB6","first-page":"167","volume-title":"Am J Respir Crit Care Med","year":"2000"},{"key":"2026032101493543500_BIB7","first-page":"37","volume-title":"Thorax","year":"2003"},{"key":"2026032101493543500_BIB8","first-page":"2472","volume-title":"Respir Med","year":"2007"},{"key":"2026032101493543500_BIB9","first-page":"1159","volume-title":"Am J Respir Crit Care Med","year":"1997"},{"key":"2026032101493543500_BIB10","first-page":"1875","volume-title":"J Infect Dis","year":"2000"},{"key":"2026032101493543500_BIB11","first-page":"645","volume-title":"Am J Respir Crit Care Med","year":"2005"},{"key":"2026032101493543500_BIB12","first-page":"549","volume-title":"J Clin Invest","year":"1995"},{"key":"2026032101493543500_BIB13","first-page":"1220","volume-title":"Am J Respir Cell Mol Biol","year":"1999"},{"key":"2026032101493543500_BIB14","first-page":"5211","volume-title":"J Immunol","year":"2000"},{"key":"2026032101493543500_BIB15","first-page":"36952","volume-title":"J Biol Chem","year":"2005"},{"key":"2026032101493543500_BIB16","first-page":"4188","volume-title":"Infect Immun","year":"2004"},{"key":"2026032101493543500_BIB17","first-page":"3561","volume-title":"J Virol","year":"1993"},{"key":"2026032101493543500_BIB18","first-page":"1111","volume-title":"Am J Respir Crit Care Med","year":"2008"},{"key":"2026032101493543500_BIB19","first-page":"L1021","volume-title":"Am J Physiol Lung Cell Mol Physiol","year":"2007"},{"key":"2026032101493543500_BIB20","first-page":"997","volume-title":"J Allergy Clin Immunol","year":"2001"},{"key":"2026032101493543500_BIB21","first-page":"1885","volume-title":"J Infect Dis","year":"2000"},{"key":"2026032101493543500_BIB22","first-page":"L1115","volume-title":"Am J Physiol","year":"2001"},{"key":"2026032101493543500_BIB23","first-page":"1967","volume-title":"N Engl J Med","year":"2005"},{"key":"2026032101493543500_BIB24","first-page":"141","volume-title":"Am J Respir Crit Care Med","year":"2004"},{"key":"2026032101493543500_BIB25","first-page":"7","volume-title":"J Exp Med","year":"2006"},{"key":"2026032101493543500_BIB26","first-page":"619","volume-title":"J Pathol","year":"2000"},{"key":"2026032101493543500_BIB27","first-page":"590","volume-title":"Thorax","year":"2002"},{"key":"2026032101493543500_BIB28","first-page":"596","volume-title":"Pulm Pharmacol Ther","year":"2007"},{"key":"2026032101493543500_BIB29","first-page":"813","volume-title":"Am J Respir Crit Care Med","year":"1996"},{"key":"2026032101493543500_BIB30","first-page":"669","volume-title":"Free Radic Biol Med","year":"1996"},{"key":"2026032101493543500_BIB31","first-page":"556","volume-title":"Eur Respir J","year":"2002"},{"key":"2026032101493543500_BIB32","first-page":"705","volume-title":"Antioxid Redox Signal","year":"2008"},{"key":"2026032101493543500_BIB33","first-page":"861","volume-title":"Am J Respir Crit Care Med","year":"2008"},{"key":"2026032101493543500_BIB34","first-page":"196","volume-title":"Thorax","year":"2006"},{"key":"2026032101493543500_BIB35","first-page":"534","volume-title":"Biochem Biophys Res Commun","year":"2004"},{"key":"2026032101493543500_BIB36","first-page":"14461","volume-title":"Proc Natl Acad Sci USA","year":"2004"},{"key":"2026032101493543500_BIB37","first-page":"937","volume-title":"J Exp Med","year":"2005"},{"key":"2026032101493543500_BIB38","first-page":"1023","volume-title":"Nat Med","year":"2006"},{"key":"2026032101493543500_BIB39","first-page":"69","volume-title":"Mucosal Immunol","year":"2010"},{"key":"2026032101493543500_BIB40","first-page":"1384","volume-title":"J Allergy Clin Immunol","year":"2009"},{"key":"2026032101493543500_BIB41","first-page":"58","volume-title":"J Virol","year":"2009"},{"key":"2026032101493543500_BIB42","first-page":"3467","volume-title":"J Virol","year":"1999"},{"key":"2026032101493543500_BIB43","first-page":"235","volume-title":"J Allergy Clin Immunol","year":"2001"},{"key":"2026032101493543500_BIB44","first-page":"697","volume-title":"J Allergy Clin Immunol","year":"2004"},{"key":"2026032101493543500_BIB45","first-page":"2121","volume-title":"FASEB J","year":"2006"},{"key":"2026032101493543500_BIB46","first-page":"113","volume-title":"Eur Respir J","year":"2006"}],"container-title":["American Journal of Respiratory and Critical Care Medicine"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/academic.oup.com\/ajrccm\/article-pdf\/182\/3\/332\/67306133\/ajrccm_182_3_332.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"https:\/\/academic.oup.com\/ajrccm\/article-pdf\/182\/3\/332\/67306133\/ajrccm_182_3_332.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,3,21]],"date-time":"2026-03-21T05:49:42Z","timestamp":1774072182000},"score":1,"resource":{"primary":{"URL":"https:\/\/academic.oup.com\/ajrccm\/article\/182\/3\/332\/8515014"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2010,8,1]]},"references-count":46,"journal-issue":{"issue":"3","published-online":{"date-parts":[[2010,8,1]]},"published-print":{"date-parts":[[2010,8,1]]}},"URL":"https:\/\/doi.org\/10.1164\/rccm.200911-1673oc","relation":{"has-review":[{"id-type":"doi","id":"10.3410\/f.3024956.5106054","asserted-by":"object"},{"id-type":"doi","id":"10.3410\/f.3024956.2703054","asserted-by":"object"}]},"ISSN":["1073-449X","1535-4970"],"issn-type":[{"value":"1073-449X","type":"print"},{"value":"1535-4970","type":"electronic"}],"subject":[],"published-other":{"date-parts":[[2010,8]]},"published":{"date-parts":[[2010,8,1]]}}}