{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,8]],"date-time":"2026-03-08T00:04:13Z","timestamp":1772928253569,"version":"3.50.1"},"reference-count":42,"publisher":"Oxford University Press (OUP)","issue":"2","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:p>Human rhinovirus (HRV) infections up-regulate proinflammatory mediators and growth factors that are associated with exacerbations of inflammatory airway diseases, such as asthma and chronic obstructive pulmonary disease (COPD). Matrix metalloproteinase (MMP)-9 was shown to be increased in the airways of patients with asthma and COPD. We sought to determine whether HRV infection modulated the expression of MMP-9 and its highest-affinity inhibitor, the tissue inhibitor of metalloproteinase (TIMP)-1, and we explored the mechanism by which this modulation occurs. In vitro studies, using RT-PCR, ELISA, zymography, and a fluorescent activity assay, demonstrated that MMP-9 mRNA, protein, and activity were increased upon infection with HRV, whereas TIMP-1 mRNA and protein remained unchanged. These results were verified in vivo, using nasal lavage samples obtained from subjects with confirmed rhinovirus infections. Human rhinovirus infections were shown to up-regulate NF-\u03baB, and NF-\u03baB has also been reported to play a role in the expression of MMP-9. We therefore investigated the role of NF-\u03baB in HRV-induced MMP-9 expression. Using two inhibitors of I\u03baB\u03b1 kinase \u03b2, we observed a concentration-dependent decrease in HRV-induced MMP-9 expression. The role of NF-\u03baB in HRV-induced MMP-9 expression was further confirmed using MMP-9 promoter luciferase constructs, which demonstrated that an NF-\u03baB site at \u2212620\/\u2212607 base pairs was necessary for HRV-induced MMP-9 expression. Electrophoretic mobility shift assays and supershift assays confirmed the nuclear translocation and binding of p50\/p65 NF-\u03baB subunits to an MMP-9\u2013specific NF-\u03baB oligonucleotide. This increase in MMP-9 may be a mechanism by which rhinovirus infections contribute to airway inflammation and, potentially, to airway remodeling.<\/jats:p>","DOI":"10.1165\/rcmb.2009-0216oc","type":"journal-article","created":{"date-parts":[[2009,9,25]],"date-time":"2009-09-25T22:04:22Z","timestamp":1253916262000},"page":"201-209","source":"Crossref","is-referenced-by-count":59,"title":["Human Rhinovirus Infection Up-Regulates MMP-9 Production in Airway Epithelial Cells via NF-\u03baB"],"prefix":"10.1093","volume":"43","author":[{"given":"Claire E.","family":"Tacon","sequence":"first","affiliation":[{"name":"Department of Medicine"},{"name":"Department of Physiology and Pharmacology, and"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Shahina","family":"Wiehler","sequence":"additional","affiliation":[{"name":"Department of Physiology and Pharmacology, and"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Neil S.","family":"Holden","sequence":"additional","affiliation":[{"name":"Department of Anatomy and Cell Biology, Airway Inflammation Research Group, Snyder Institute of Infection, Immunity, and Inflammation, University of Calgary, Calgary, Alberta, Canada"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Robert","family":"Newton","sequence":"additional","affiliation":[{"name":"Department of Anatomy and Cell Biology, Airway Inflammation Research Group, Snyder Institute of Infection, Immunity, and Inflammation, University of Calgary, Calgary, Alberta, Canada"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"David","family":"Proud","sequence":"additional","affiliation":[{"name":"Department of Physiology and Pharmacology, and"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Richard","family":"Leigh","sequence":"additional","affiliation":[{"name":"Department of Medicine"},{"name":"Department of Physiology and Pharmacology, 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