{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,15]],"date-time":"2026-07-15T14:45:00Z","timestamp":1784126700678,"version":"3.55.0"},"reference-count":35,"publisher":"American Physiological Society","issue":"5","funder":[{"DOI":"10.13039\/501100000024","name":"Gouvernement du Canada | Canadian Institutes of Health Research (Instituts de recherche en sant\u00e9 du Canada)","doi-asserted-by":"publisher","award":["43923"],"award-info":[{"award-number":["43923"]}],"id":[{"id":"10.13039\/501100000024","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100000024","name":"Gouvernement du Canada | Canadian Institutes of Health Research (Instituts de recherche en sant\u00e9 du Canada)","doi-asserted-by":"publisher","award":["82049"],"award-info":[{"award-number":["82049"]}],"id":[{"id":"10.13039\/501100000024","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["American Journal of Physiology-Lung Cellular and Molecular Physiology"],"published-print":{"date-parts":[[2017,5,1]]},"abstract":"<jats:p>Exacerbations of chronic obstructive pulmonary disease are triggered by viral or bacterial pathogens, with human rhinovirus (HRV) and nontypeable Hemophilus influenzae (NTHI) among the most commonly detected pathogens. Patients who suffer from concomitant viral and bacterial infection have more severe exacerbations. The airway epithelial cell is the initial site of viral and bacterial interactions, and CCL20 is an epithelial chemokine that attracts immature dendritic cells to the airways and can act as an antimicrobial. As such, it contributes to innate and adaptive immune responses to infection. We used primary cultures of human bronchial epithelial cells and the BEAS-2B cell line to examine the effects of bacterial-viral coexposure, as well as each stimulus alone, on epithelial expression of CXCL8 and, in particular, CCL20. HRV-bacterial coexposure induced synergistic production of CXCL8 and CCL20 compared with the sum of each stimulus alone. Synergistic induction of CCL20 did not require viral replication and occurred with two different HRV serotypes that use different viral receptors. Synergy was also seen with either NTHI or Pseudomonas aeruginosa. Synergistic induction of CCL20 was transcriptionally regulated. Although NF-\u03baB was required for transcription, it did not regulate synergy, but NF-IL-6 did appear to contribute. Among MAPK inhibitors studied, neither SB203580 nor PD98059 had any effect on synergy, whereas U0126 prevented synergistic induction of CCL20 by HRV and bacteria, apparently via \u201coff-target\u201d effects. Thus bacterial-viral coexposure synergistically increases innate immune responses compared with individual infections. We speculate that this increased inflammatory response leads to worse clinical outcomes.<\/jats:p>","DOI":"10.1152\/ajplung.00362.2016","type":"journal-article","created":{"date-parts":[[2017,3,11]],"date-time":"2017-03-11T01:20:19Z","timestamp":1489195219000},"page":"L731-L740","source":"Crossref","is-referenced-by-count":18,"title":["Rhinovirus-bacteria coexposure synergistically induces CCL20 production from human bronchial epithelial cells"],"prefix":"10.1152","volume":"312","author":[{"given":"Barbara A.","family":"Maciejewski","sequence":"first","affiliation":[{"name":"Department of Physiology &amp; Pharmacology, Snyder Institute for Chronic Diseases, Cumming School of Medicine, University of Calgary, Calgary, Alberta, Canada; and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kyla C.","family":"Jamieson","sequence":"additional","affiliation":[{"name":"Department of Physiology &amp; Pharmacology, Snyder Institute for Chronic Diseases, Cumming School of Medicine, University of Calgary, Calgary, Alberta, Canada; and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jason W.","family":"Arnason","sequence":"additional","affiliation":[{"name":"Department of Physiology &amp; Pharmacology, Snyder Institute for Chronic Diseases, Cumming School of Medicine, University of Calgary, Calgary, Alberta, Canada; and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Cora","family":"Kooi","sequence":"additional","affiliation":[{"name":"Department of Physiology &amp; Pharmacology, Snyder Institute for Chronic Diseases, Cumming School of Medicine, University of Calgary, Calgary, Alberta, Canada; and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shahina","family":"Wiehler","sequence":"additional","affiliation":[{"name":"Department of Physiology &amp; Pharmacology, Snyder Institute for Chronic Diseases, Cumming School of Medicine, University of Calgary, Calgary, Alberta, Canada; and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Suzanne L.","family":"Traves","sequence":"additional","affiliation":[{"name":"Department of Physiology &amp; Pharmacology, Snyder Institute for Chronic Diseases, Cumming School of Medicine, University of Calgary, Calgary, Alberta, Canada; and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Richard","family":"Leigh","sequence":"additional","affiliation":[{"name":"Department of Physiology &amp; Pharmacology, Snyder Institute for Chronic Diseases, Cumming School of Medicine, University of Calgary, Calgary, Alberta, Canada; and"},{"name":"Department of Medicine, Snyder Institute for Chronic Diseases, Cumming School of Medicine, University of Calgary, Calgary, Alberta, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"David","family":"Proud","sequence":"additional","affiliation":[{"name":"Department of Physiology &amp; Pharmacology, Snyder Institute for Chronic Diseases, Cumming School of Medicine, University of Calgary, Calgary, Alberta, Canada; and"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"24","reference":[{"key":"B1","doi-asserted-by":"publisher","DOI":"10.1038\/nri1391"},{"key":"B2","doi-asserted-by":"publisher","DOI":"10.1042\/BJ20070797"},{"key":"B3","doi-asserted-by":"publisher","DOI":"10.1189\/jlb.0607349"},{"key":"B4","doi-asserted-by":"publisher","DOI":"10.1183\/09031936.00109906"},{"key":"B5","doi-asserted-by":"publisher","DOI":"10.1164\/ajrccm\/140.2.449"},{"key":"B6","doi-asserted-by":"publisher","DOI":"10.1038\/nm.3049"},{"key":"B7","doi-asserted-by":"publisher","DOI":"10.1042\/bj3510095"},{"key":"B8","doi-asserted-by":"publisher","DOI":"10.1111\/irv.12174"},{"key":"B9","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.273.29.18623"},{"key":"B10","first-page":"235","volume":"5","author":"Guarascio AJ","year":"2013","journal-title":"Clinicoecon Outcomes Res"},{"key":"B11","doi-asserted-by":"publisher","DOI":"10.1016\/j.jaci.2009.04.041"},{"key":"B12","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(12)61728-0"},{"key":"B13","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.90.21.10193"},{"key":"B14","doi-asserted-by":"publisher","DOI":"10.1016\/j.rmed.2008.06.006"},{"key":"B15","doi-asserted-by":"publisher","DOI":"10.1124\/jpet.106.118125"},{"key":"B16","doi-asserted-by":"publisher","DOI":"10.1164\/rccm.200506-859OC"},{"key":"B17","doi-asserted-by":"publisher","DOI":"10.1136\/thorax.57.9.759"},{"key":"B18","doi-asserted-by":"publisher","DOI":"10.1164\/ajrccm.163.5.2101039"},{"key":"B19","doi-asserted-by":"publisher","DOI":"10.1111\/j.1600-065X.2011.01033.x"},{"key":"B20","doi-asserted-by":"crossref","first-page":"934","DOI":"10.1128\/JVI.72.2.934-942.1998","volume":"72","author":"Sanders SP","year":"1998","journal-title":"J Virol"},{"key":"B21","doi-asserted-by":"publisher","DOI":"10.1002\/1521-4141(200212)32:12<3515::AID-IMMU3515>3.0.CO;2-3"},{"key":"B22","doi-asserted-by":"publisher","DOI":"10.1016\/S1359-6101(03)00049-2"},{"key":"B23","doi-asserted-by":"publisher","DOI":"10.1164\/ajrccm.164.9.2105011"},{"key":"B24","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMra0800353"},{"key":"B25","doi-asserted-by":"publisher","DOI":"10.1136\/thx.2005.040527"},{"key":"B26","doi-asserted-by":"publisher","DOI":"10.1165\/rcmb.2002-0272OC"},{"key":"B27","doi-asserted-by":"publisher","DOI":"10.1172\/JCI118067"},{"key":"B28","doi-asserted-by":"publisher","DOI":"10.1016\/j.jcf.2005.05.011"},{"key":"B29","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.177.10.6859"},{"key":"B30","doi-asserted-by":"publisher","DOI":"10.1111\/resp.12099"},{"key":"B31","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(07)61382-8"},{"key":"B32","doi-asserted-by":"publisher","DOI":"10.1152\/ajplung.00066.2007"},{"key":"B33","doi-asserted-by":"publisher","DOI":"10.1378\/chest.129.2.317"},{"key":"B34","doi-asserted-by":"publisher","DOI":"10.1164\/rccm.200210-1179OC"},{"key":"B35","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.0802401"}],"container-title":["American Journal of Physiology-Lung Cellular and Molecular Physiology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.physiology.org\/doi\/pdf\/10.1152\/ajplung.00362.2016","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2020,10,3]],"date-time":"2020-10-03T18:49:52Z","timestamp":1601750992000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.physiology.org\/doi\/10.1152\/ajplung.00362.2016"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2017,5,1]]},"references-count":35,"journal-issue":{"issue":"5","published-print":{"date-parts":[[2017,5,1]]}},"alternative-id":["10.1152\/ajplung.00362.2016"],"URL":"https:\/\/doi.org\/10.1152\/ajplung.00362.2016","relation":{},"ISSN":["1040-0605","1522-1504"],"issn-type":[{"value":"1040-0605","type":"print"},{"value":"1522-1504","type":"electronic"}],"subject":[],"published":{"date-parts":[[2017,5,1]]}}}