{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,22]],"date-time":"2026-09-22T17:09:23Z","timestamp":1790096963012,"version":"4.0.1"},"reference-count":44,"publisher":"Wiley","issue":"9","license":[{"start":{"date-parts":[[2018,7,31]],"date-time":"2018-07-31T00:00:00Z","timestamp":1532995200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Clin Experimental Allergy"],"published-print":{"date-parts":[[2018,9]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Background<\/jats:title><jats:p>Viral infection of the bronchial epithelium disrupts the barrier properties of the epithelium in healthy individuals and those with lung disease. Repair of the bronchial epithelium is dependent of the formation of a provisional fibrin matrix and migration of epithelial cells to cover denuded areas, followed by proliferation and differentiation.<\/jats:p><\/jats:sec><jats:sec><jats:title>Objective<\/jats:title><jats:p>The objective was to test the hypothesis that poly I:C, a model of viral infection, limits epithelial repair through the stimulated release of matrix metalloproteinase\u201013 (<jats:styled-content style=\"fixed-case\">MMP<\/jats:styled-content>\u201013).<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>Confluent layers of cultured normal human primary bronchial epithelial cells (<jats:styled-content style=\"fixed-case\">NHBE<\/jats:styled-content>) and <jats:styled-content style=\"fixed-case\">SV<\/jats:styled-content>\u201040 virus\u2010transformed 16<jats:styled-content style=\"fixed-case\">HBE<\/jats:styled-content>14o\u2010 bronchial epithelial cells were mechanically wounded, and video microscopy used to measure the rate of wound closure over 2 hours, in the absence and presence of poly I:C (1\u201020 \u03bcg\/mL). <jats:styled-content style=\"fixed-case\">MMP<\/jats:styled-content>\u201013, tissue factor and endothelin release were measured by <jats:styled-content style=\"fixed-case\">ELISA<\/jats:styled-content>. The effect of inhibitors of <jats:styled-content style=\"fixed-case\">MMP<\/jats:styled-content>\u201013 activity and expression and a nonspecific endothelin receptor antagonist, bosentan, on the rate of epithelial repair was investigated.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Poly I:C limited the rate of epithelial repair, and <jats:styled-content style=\"fixed-case\">NHBE<\/jats:styled-content> were significantly more sensitive to poly I:C effects than 16<jats:styled-content style=\"fixed-case\">HBE<\/jats:styled-content>14o\u2010 cells. <jats:styled-content style=\"fixed-case\">NHBE<\/jats:styled-content>, but not 16<jats:styled-content style=\"fixed-case\">HBE<\/jats:styled-content>14o\u2010, released <jats:styled-content style=\"fixed-case\">MMP<\/jats:styled-content>\u201013 in response to poly I:C. Inhibitors of <jats:styled-content style=\"fixed-case\">MMP<\/jats:styled-content>\u201013 activity (<jats:styled-content style=\"fixed-case\">WAY<\/jats:styled-content> 170523) and expression (dimethyl fumarate) significantly enhanced the rate of repair. Bosentan enhanced the rate of bronchial epithelial repair by a mechanism that was independent of <jats:styled-content style=\"fixed-case\">MMP<\/jats:styled-content>\u201013.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions and clinical relevance<\/jats:title><jats:p>Bronchial epithelial repair is limited by endothelin and by <jats:styled-content style=\"fixed-case\">MMP<\/jats:styled-content>\u201013, a protease that degrades coagulation factors, such as fibrinogen, and matrix proteins essential for epithelial repair. Further studies with primary cells from patients are needed to confirm whether repurposing bosentan and inhibitors of <jats:styled-content style=\"fixed-case\">MMP<\/jats:styled-content>\u201013 expression or activity, for inhalation may be a useful therapeutic strategy in diseases where repeated cycles of epithelial injury and repair occur, such as asthma and <jats:styled-content style=\"fixed-case\">COPD<\/jats:styled-content>.<\/jats:p><\/jats:sec>","DOI":"10.1111\/cea.13215","type":"journal-article","created":{"date-parts":[[2018,6,20]],"date-time":"2018-06-20T20:48:53Z","timestamp":1529527733000},"page":"1214-1221","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":9,"title":["Targeting matrix metalloproteinase\u201013 in bronchial epithelial repair"],"prefix":"10.1111","volume":"48","author":[{"given":"Christopher","family":"Howell","sequence":"first","affiliation":[{"name":"School of Pharmacy and Biomedical Sciences 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