{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,31]],"date-time":"2026-10-31T01:26:29Z","timestamp":1793409989311,"version":"4.5.0"},"reference-count":79,"publisher":"American Society for Clinical Investigation","issue":"24","funder":[{"DOI":"10.13039\/100000060","name":"NIAID","doi-asserted-by":"crossref","award":["AI111475-01"],"award-info":[{"award-number":["AI111475-01"]}],"id":[{"id":"10.13039\/100000060","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/100000050","name":"NHLBI","doi-asserted-by":"crossref","award":["HL086814"],"award-info":[{"award-number":["HL086814"]}],"id":[{"id":"10.13039\/100000050","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/100000050","name":"NHLBI","doi-asserted-by":"crossref","award":["HL063137"],"award-info":[{"award-number":["HL063137"]}],"id":[{"id":"10.13039\/100000050","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/100000060","name":"NIAID","doi-asserted-by":"crossref","award":["AI123516"],"award-info":[{"award-number":["AI123516"]}],"id":[{"id":"10.13039\/100000060","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/100005640","name":"Flight Attendants medical Research Institute","doi-asserted-by":"crossref","award":["CIA123046"],"award-info":[{"award-number":["CIA123046"]}],"id":[{"id":"10.13039\/100005640","id-type":"DOI","asserted-by":"crossref"}]},{"name":"U.S. Department of Defense","award":["PR152060"],"award-info":[{"award-number":["PR152060"]}]},{"DOI":"10.13039\/100000050","name":"NHLBI","doi-asserted-by":"crossref","award":["POI HL105339"],"award-info":[{"award-number":["POI HL105339"]}],"id":[{"id":"10.13039\/100000050","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/100000050","name":"NHBLI","doi-asserted-by":"crossref","award":["P01 HL114501"],"award-info":[{"award-number":["P01 HL114501"]}],"id":[{"id":"10.13039\/100000050","id-type":"DOI","asserted-by":"crossref"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2018,12,20]]},"abstract":"<jats:p>\n                    Matrix metalloproteinase-9 (MMP-9) cleaves various proteins to regulate inflammatory and injury responses. However, MMP-9\u2019s activities during influenza A viral (IAV) infections are incompletely understood. Herein, plasma MMP-9 levels were increased in patients with pandemic H1N1 and seasonal IAV infections. MMP-9 lung levels were increased and localized to airway epithelial cells and leukocytes in H1N1-infected WT murine lungs. H1N1-infected\n                    <jats:italic>\n                      Mmp-9\n                      <jats:sup>\u2013\/\u2013<\/jats:sup>\n                    <\/jats:italic>\n                    mice had lower mortality rates, reduced weight loss, lower lung viral titers, and reduced lung injury, along with lower E-cadherin shedding in bronchoalveolar lavage fluid (BALF) samples than WT mice. H1N1-infected\n                    <jats:italic>\n                      Mmp-9\n                      <jats:sup>\u2013\/\u2013<\/jats:sup>\n                    <\/jats:italic>\n                    mice had an altered immune response to IAV with lower BALF PMN and macrophage counts, higher Th1-like CD4\n                    <jats:sup>+<\/jats:sup>\n                    and CD8\n                    <jats:sup>+<\/jats:sup>\n                    T cell subsets, lower T regulatory cell counts, reduced lung type I interferon levels, and higher lung interferon-\u03b3 levels.\n                    <jats:italic>Mmp-9<\/jats:italic>\n                    bone marrow\u2013chimera studies revealed that Mmp-9 deficiency in lung parenchymal cells protected mice from IAV-induced mortality. H1N1-infected\n                    <jats:italic>\n                      Mmp-9\n                      <jats:sup>\u2013\/\u2013<\/jats:sup>\n                    <\/jats:italic>\n                    lung epithelial cells had lower viral titers than H1N1-infected WT cells in vitro. Thus, H1N1-infected\n                    <jats:italic>\n                      Mmp-9\n                      <jats:sup>\u2013\/\u2013<\/jats:sup>\n                    <\/jats:italic>\n                    mice are protected from IAV-induced lung disease due to a more effective adaptive immune response to IAV and reduced epithelial barrier injury due partly to reduced E-cadherin shedding. Thus, we believe that MMP-9 is a novel therapeutic target for IAV infections.\n                  <\/jats:p>","DOI":"10.1172\/jci.insight.99022","type":"journal-article","created":{"date-parts":[[2018,12,19]],"date-time":"2018-12-19T11:02:38Z","timestamp":1545217358000},"source":"Crossref","is-referenced-by-count":54,"title":["Matrix metalloproteinase-9 deficiency protects mice from severe influenza A viral infection"],"prefix":"10.1172","volume":"3","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-4994-075X","authenticated-orcid":true,"given":"Joselyn","family":"Rojas-Quintero","sequence":"first","affiliation":[{"name":"Division of Pulmonary and Critical Care Medicine, Brigham and Women\u2019s Hospital, and Harvard Medical School, Boston, Massachusetts, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9900-740X","authenticated-orcid":true,"given":"Xiaoyun","family":"Wang","sequence":"additional","affiliation":[{"name":"Division of Pulmonary and Critical Care Medicine, Brigham and Women\u2019s Hospital, and Harvard Medical School, Boston, Massachusetts, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jennifer","family":"Tipper","sequence":"additional","affiliation":[{"name":"Department of Anesthesiology and Perioperative Medicine, Division of Molecular and Translational Biomedicine, School of Medicine, University of Alabama-Birmingham, Birmingham, Alabama, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Patrick R.","family":"Burkett","sequence":"additional","affiliation":[{"name":"Division of Pulmonary and Critical Care Medicine, Brigham and Women\u2019s Hospital, and Harvard Medical School, Boston, Massachusetts, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Joaquin","family":"Zu\u00f1iga","sequence":"additional","affiliation":[{"name":"Laboratory of Immunobiology and Genetics, and Intensive Care Unit, Instituto Nacional de Enfermedades Respiratorias Ismael Cos\u00edo Villegas, Mexico City, Mexico."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Amit R.","family":"Ashtekar","sequence":"additional","affiliation":[{"name":"Department of Anesthesiology and Perioperative Medicine, Division of Molecular and Translational Biomedicine, School of Medicine, University of Alabama-Birmingham, Birmingham, Alabama, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Francesca","family":"Polverino","sequence":"additional","affiliation":[{"name":"Division of Pulmonary and Critical Care Medicine, Brigham and Women\u2019s Hospital, and Harvard Medical School, Boston, Massachusetts, USA."},{"name":"Lovelace Respiratory Research Institute, Albuquerque, New Mexico, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Amit","family":"Rout","sequence":"additional","affiliation":[{"name":"Division of Pulmonary and Critical Care Medicine, Brigham and Women\u2019s Hospital, and Harvard Medical School, Boston, Massachusetts, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ilyas","family":"Yambayev","sequence":"additional","affiliation":[{"name":"Division of Pulmonary and Critical Care Medicine, Brigham and Women\u2019s Hospital, and Harvard Medical School, Boston, Massachusetts, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Carmen","family":"Hern\u00e1ndez","sequence":"additional","affiliation":[{"name":"Laboratory of Immunobiology and Genetics, and Intensive Care Unit, Instituto Nacional de Enfermedades Respiratorias Ismael Cos\u00edo Villegas, Mexico City, Mexico."},{"name":"Escuela de Medicina y Ciencias de la Salud, Tecnologico de Monterrey, Mexico City, Mexico."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Luis","family":"Jimenez","sequence":"additional","affiliation":[{"name":"Laboratory of Immunobiology and Genetics, and Intensive Care Unit, Instituto Nacional de Enfermedades Respiratorias Ismael Cos\u00edo Villegas, Mexico City, Mexico."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gustavo","family":"Ram\u00edrez","sequence":"additional","affiliation":[{"name":"Laboratory of Immunobiology and Genetics, and Intensive Care Unit, Instituto Nacional de Enfermedades Respiratorias Ismael Cos\u00edo Villegas, Mexico City, Mexico."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kevin S.","family":"Harrod","sequence":"additional","affiliation":[{"name":"Department of Anesthesiology and Perioperative Medicine, Division of Molecular and Translational Biomedicine, School of Medicine, University of Alabama-Birmingham, Birmingham, Alabama, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Caroline A.","family":"Owen","sequence":"additional","affiliation":[{"name":"Division of Pulmonary and Critical Care Medicine, Brigham and Women\u2019s Hospital, and Harvard Medical School, Boston, Massachusetts, USA."},{"name":"Lovelace Respiratory Research Institute, Albuquerque, New Mexico, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"232","published-online":{"date-parts":[[2018,12,20]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","DOI":"10.1007\/s13224-011-0055-2"},{"key":"B2","doi-asserted-by":"publisher","DOI":"10.1128\/MMBR.05015-11"},{"key":"B3","doi-asserted-by":"publisher","DOI":"10.1016\/j.jtbi.2011.08.003"},{"key":"B4","doi-asserted-by":"publisher","DOI":"10.15585\/mmwr.ss6611a1"},{"key":"B5","doi-asserted-by":"publisher","DOI":"10.1093\/intimm\/dxr123"},{"key":"B6","doi-asserted-by":"publisher","DOI":"10.2215\/CJN.02160311"},{"key":"B7","doi-asserted-by":"publisher","DOI":"10.1053\/spid.2002.122999"},{"issue":"4 Pt B","key":"B8","doi-asserted-by":"crossref","first-page":"593","DOI":"10.1177\/135965350701200S07.1","article-title":"Neuraminidase inhibitors and their role in avian and pandemic influenza","volume":"12","author":"Crusat","year":"2007","journal-title":"Antivir Ther (Lond)"},{"issue":"6\u20137","key":"B9","doi-asserted-by":"crossref","first-page":"1246","DOI":"10.1016\/j.biocel.2008.01.020","article-title":"Leukocyte cell surface proteinases: regulation of expression, functions, and mechanisms of surface localization","volume":"40","author":"Owen","year":"2008","journal-title":"Int J Biochem Cell Biol"},{"key":"B10","doi-asserted-by":"publisher","DOI":"10.1165\/rcmb.2006-0040OC"},{"issue":"5 Pt 1","key":"B11","first-page":"L813","article-title":"Localization and activation of type IV collagenase\/gelatinase at endothelial focal contacts","volume":"272","author":"Partridge","year":"1997","journal-title":"Am J Physiol"},{"issue":"3 Pt 1","key":"B12","doi-asserted-by":"crossref","first-page":"283","DOI":"10.1165\/rcmb.2003-0034OC","article-title":"Inducible expression of tissue inhibitor of metalloproteinases-resistant matrix metalloproteinase-9 on the cell surface of neutrophils","volume":"29","author":"Owen","year":"2003","journal-title":"Am J Respir Cell Mol Biol"},{"key":"B13","doi-asserted-by":"publisher","DOI":"10.1002\/jlb.65.2.137"},{"issue":"Pt 1","key":"B14","doi-asserted-by":"crossref","first-page":"55","DOI":"10.1042\/bj3290055","article-title":"Binding of urokinase-type plasminogen activator-plasminogen activator inhibitor-1 complex to the endocytosis receptors alpha2-macroglobulin receptor\/low-density lipoprotein receptor-related protein and very-low-density lipoprotein receptor involves basic residues in the inhibitor","volume":"329","author":"Rodenburg","year":"1998","journal-title":"Biochem J"},{"key":"B15","doi-asserted-by":"publisher","DOI":"10.1096\/fj.03-1412fje"},{"key":"B16","doi-asserted-by":"publisher","DOI":"10.1152\/ajplung.00270.2005"},{"key":"B17","doi-asserted-by":"publisher","DOI":"10.1152\/ajplung.00334.2007"},{"key":"B18","doi-asserted-by":"publisher","DOI":"10.1152\/ajplung.90578.2008"},{"key":"B19","doi-asserted-by":"publisher","DOI":"10.1158\/0008-5472.CAN-07-5046"},{"key":"B20","doi-asserted-by":"publisher","DOI":"10.1038\/35036374"},{"key":"B21","doi-asserted-by":"publisher","DOI":"10.1016\/S0002-9440(10)64563-4"},{"issue":"23","key":"B22","first-page":"2526","article-title":"Acute respiratory distress syndrome: the Berlin Definition","volume":"307","author":"ARDS Definition Task Force","year":"2012","journal-title":"JAMA"},{"key":"B23","doi-asserted-by":"publisher","DOI":"10.2741\/4031"},{"key":"B24","doi-asserted-by":"publisher","DOI":"10.1016\/S0002-9440(10)64318-0"},{"key":"B25","doi-asserted-by":"publisher","DOI":"10.1016\/S0022-2143(99)90148-8"},{"key":"B26","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0050300"},{"key":"B27","doi-asserted-by":"publisher","DOI":"10.1038\/cmi.2015.74"},{"key":"B28","doi-asserted-by":"publisher","DOI":"10.1086\/656044"},{"issue":"1","key":"B29","doi-asserted-by":"crossref","first-page":"186","DOI":"10.1016\/j.bbapap.2011.07.001","article-title":"Role of host cellular proteases in the pathogenesis of influenza and influenza-induced multiple organ failure","volume":"1824","author":"Kido","year":"2012","journal-title":"Biochim Biophys Acta"},{"issue":"2\u20133","key":"B30","doi-asserted-by":"crossref","first-page":"171","DOI":"10.1016\/S1359-6101(00)00026-5","article-title":"Molecular pathogenesis of influenza A virus infection and virus-induced regulation of cytokine gene expression","volume":"12","author":"Julkunen","year":"2001","journal-title":"Cytokine Growth Factor Rev"},{"key":"B31","doi-asserted-by":"crossref","DOI":"10.3389\/fimmu.2017.01177","article-title":"Mucosa-associated lymphoid tissue lymphoma translocation protein 1 positively modulates matrix metalloproteinase-9 production in alveolar macrophages upon Toll-like receptor 7 signaling and influenza virus infection","volume":"8","author":"Lee","year":"2017","journal-title":"Front Immunol"},{"key":"B32","doi-asserted-by":"publisher","DOI":"10.1038\/mi.2014.54"},{"key":"B33","doi-asserted-by":"publisher","DOI":"10.1165\/rcmb.2015-0020TR"},{"key":"B34","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.0900290"},{"key":"B35","doi-asserted-by":"publisher","DOI":"10.1183\/09031936.00186214"},{"key":"B36","doi-asserted-by":"publisher","DOI":"10.1038\/nri3581"},{"key":"B37","doi-asserted-by":"publisher","DOI":"10.1016\/j.cytogfr.2014.07.015"},{"key":"B38","doi-asserted-by":"publisher","DOI":"10.1038\/nrrheum.2009.237"},{"key":"B39","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.178.12.7616"},{"key":"B40","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.167.4.2004"},{"key":"B41","doi-asserted-by":"publisher","DOI":"10.1038\/cmi.2017.10"},{"key":"B42","first-page":"423","article-title":"The effector T cell response to influenza infection","volume":"386","author":"Hufford","year":"2015","journal-title":"Curr Top Microbiol Immunol"},{"key":"B43","doi-asserted-by":"publisher","DOI":"10.1038\/nm.3508"},{"key":"B44","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2011.08.015"},{"issue":"3\u20134","key":"B45","doi-asserted-by":"crossref","first-page":"293","DOI":"10.2119\/molmed.2010.00138","article-title":"Contribution of neutrophils to acute lung injury","volume":"17","author":"Grommes","year":"2011","journal-title":"Mol Med"},{"key":"B46","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.176.3.1311"},{"key":"B47","doi-asserted-by":"publisher","DOI":"10.1016\/j.immuni.2018.03.015"},{"key":"B48","doi-asserted-by":"publisher","DOI":"10.1007\/s11357-009-9100-9"},{"key":"B49","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2010-12-321588"},{"key":"B50","doi-asserted-by":"publisher","DOI":"10.1046\/j.1432-1033.2003.03760.x"},{"key":"B51","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.181.4.2806"},{"key":"B52","doi-asserted-by":"publisher","DOI":"10.1097\/SHK.0b013e31823f1776"},{"key":"B53","doi-asserted-by":"publisher","DOI":"10.1152\/ajplung.00001.2016"},{"key":"B54","doi-asserted-by":"publisher","DOI":"10.1016\/j.it.2011.03.004"},{"key":"B55","doi-asserted-by":"publisher","DOI":"10.1101\/gad.211383.112"},{"key":"B56","doi-asserted-by":"publisher","DOI":"10.1158\/0008-5472.CAN-09-4155"},{"key":"B57","doi-asserted-by":"publisher","DOI":"10.1038\/nrmicro3346"},{"key":"B58","doi-asserted-by":"publisher","DOI":"10.1016\/0042-6822(75)90284-6"},{"key":"B59","doi-asserted-by":"publisher","DOI":"10.1128\/JVI.01118-06"},{"key":"B60","doi-asserted-by":"publisher","DOI":"10.1128\/JVI.74.13.6015-6020.2000"},{"key":"B61","doi-asserted-by":"publisher","DOI":"10.1016\/j.chom.2016.09.005"},{"key":"B62","doi-asserted-by":"publisher","DOI":"10.1371\/journal.ppat.1002641"},{"key":"B63","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.0902497"},{"key":"B64","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0164247"},{"key":"B65","doi-asserted-by":"publisher","DOI":"10.1152\/ajplung.00304.2016"},{"key":"B66","doi-asserted-by":"publisher","DOI":"10.1016\/j.jaut.2017.06.009"},{"key":"B67","doi-asserted-by":"publisher","DOI":"10.1183\/09031936.00020611"},{"issue":"1 Suppl","key":"B68","doi-asserted-by":"crossref","first-page":"17S","DOI":"10.1378\/chest.116.suppl_1.17S","article-title":"Gelatinase B deficiency does not protect against lipopolysaccharide-induced acute lung injury","volume":"116","author":"Betsuyaku","year":"1999","journal-title":"Chest"},{"key":"B69","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.1202329"},{"key":"B70","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.1201043"},{"issue":"3 Suppl","key":"B71","doi-asserted-by":"crossref","first-page":"S217","DOI":"10.1097\/01.CCM.0000155788.39101.7E","article-title":"Prognostic determinants of acute respiratory distress syndrome in adults: impact on clinical trial design","volume":"33","author":"Ware","year":"2005","journal-title":"Crit Care Med"},{"key":"B72","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M608346200"},{"key":"B73","doi-asserted-by":"crossref","DOI":"10.1186\/1743-422X-3-63","article-title":"New low-viscosity overlay medium for viral plaque assays","volume":"3","author":"Matrosovich","year":"2006","journal-title":"Virol J"},{"key":"B74","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.178.12.7563"},{"issue":"95","key":"B75","doi-asserted-by":"crossref","DOI":"10.3791\/52236-v","article-title":"Automated measurement of pulmonary emphysema and small airway remodeling in cigarette smoke-exposed mice","volume":"95","author":"Laucho-Contreras","year":"2015","journal-title":"J Vis Exp"},{"key":"B76","first-page":"183","article-title":"Well-differentiated human airway epithelial cell cultures","volume":"107","author":"Fulcher","year":"2005","journal-title":"Methods Mol Med"},{"key":"B77","doi-asserted-by":"publisher","DOI":"10.1177\/2211068214561025"},{"issue":"45","key":"B78","doi-asserted-by":"crossref","DOI":"10.3791\/2445","article-title":"Detection of functional matrix metalloproteinases by zymography","author":"Hu","year":"2010","journal-title":"J Vis Exp"},{"key":"B79","doi-asserted-by":"publisher","DOI":"10.1038\/bjc.1976.220"}],"container-title":["JCI Insight"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/insight.jci.org\/articles\/view\/99022\/files\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,5,19]],"date-time":"2026-05-19T12:35:31Z","timestamp":1779194131000},"score":1,"resource":{"primary":{"URL":"https:\/\/insight.jci.org\/articles\/view\/99022"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2018,12,20]]},"references-count":79,"journal-issue":{"issue":"24","published-online":{"date-parts":[[2018,12,20]]},"published-print":{"date-parts":[[2018,12,20]]}},"alternative-id":["10.1172\/jci.insight.99022"],"URL":"https:\/\/doi.org\/10.1172\/jci.insight.99022","relation":{},"ISSN":["2379-3708"],"issn-type":[{"value":"2379-3708","type":"electronic"}],"subject":[],"published":{"date-parts":[[2018,12,20]]},"article-number":"e99022"}}