{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,10]],"date-time":"2026-09-10T18:22:54Z","timestamp":1789064574671,"version":"build-2803163510"},"reference-count":49,"publisher":"Oxford University Press (OUP)","issue":"3","license":[{"start":{"date-parts":[[2012,9,1]],"date-time":"2012-09-01T00:00:00Z","timestamp":1346457600000},"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":[[2012,9,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>Mechanical ventilation is necessary for patients with acute respiratory failure, but can cause or propagate lung injury. We previously identified cyclooxygenase-2 as a candidate gene in mechanical ventilation\u2013induced lung injury. Our objective was to determine the role of cyclooxygenase-2 in mechanical ventilation\u2013induced lung injury and the effects of cyclooxygenase-2 inhibition on lung inflammation and barrier disruption. Mice were mechanically ventilated at low and high tidal volumes, in the presence or absence of pharmacologic cyclooxygenase-2\u2013specific inhibition with 3-(4-methylsulphonylphenyl)-4-phenyl-5-trifluoromethylisoxazole (CAY10404). Lung injury was assessed using markers of alveolar\u2013capillary leakage and lung inflammation. Cyclooxygenase-2 expression and activity were measured by Western blotting, real-time PCR, and lung\/plasma prostanoid analysis, and tissue sections were analyzed for cyclooxygenase-2 staining by immunohistochemistry. High tidal volume ventilation induced lung injury, significantly increasing both lung leakage and lung inflammation relative to control and low tidal volume ventilation. High tidal volume mechanical ventilation significantly induced cyclooxygenase-2 expression and activity, both in the lungs and systemically, compared with control mice and low tidal volume mice. The immunohistochemical analysis of lung sections localized cyclooxygenase-2 expression to monocytes and macrophages in the alveoli. The pharmacologic inhibition of cyclooxygenase-2 with CAY10404 significantly decreased cyclooxygenase activity and attenuated lung injury in mice ventilated at high tidal volume, attenuating barrier disruption, tissue inflammation, and inflammatory cell signaling. This study demonstrates the induction of cyclooxygenase-2 by mechanical ventilation, and suggests that the therapeutic inhibition of cyclooxygenase-2 may attenuate ventilator-induced acute lung injury.<\/jats:p>","DOI":"10.1165\/rcmb.2011-0005oc","type":"journal-article","created":{"date-parts":[[2012,5,4]],"date-time":"2012-05-04T01:17:19Z","timestamp":1336094239000},"page":"387-394","source":"Crossref","is-referenced-by-count":23,"title":["The Role of Cyclooxygenase-2 in Mechanical Ventilation\u2013Induced Lung Injury"],"prefix":"10.1093","volume":"47","author":[{"given":"Joshua A.","family":"Robertson","sequence":"first","affiliation":[{"name":"Division of Pulmonary and Critical Care, and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"David","family":"Sauer","sequence":"additional","affiliation":[{"name":"Department of Pathology, Oregon Health and Science University, Portland, Oregon"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jeffrey A.","family":"Gold","sequence":"additional","affiliation":[{"name":"Division of Pulmonary and Critical Care, and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stephanie A.","family":"Nonas","sequence":"additional","affiliation":[{"name":"Division of Pulmonary and Critical Care, and"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2012,9,1]]},"reference":[{"key":"2026021904152586800_bib1","doi-asserted-by":"crossref","first-page":"1301","DOI":"10.1056\/NEJM200005043421801","article-title":"Ventilation with lower tidal volumes as compared with traditional tidal volumes for acute lung injury and the acute respiratory distress syndrome","volume":"342","author":"Acute Respiratory Distress Syndrome Network","year":"2000","journal-title":"N Engl J Med"},{"key":"2026021904152586800_bib2","doi-asserted-by":"crossref","first-page":"54","DOI":"10.1001\/jama.282.1.54","article-title":"Effect of mechanical ventilation on inflammatory mediators in patients with acute respiratory distress syndrome: a randomized controlled trial","volume":"282","author":"Ranieri","year":"1999","journal-title":"JAMA"},{"key":"2026021904152586800_bib3","doi-asserted-by":"crossref","first-page":"119","DOI":"10.1016\/j.vph.2008.06.009","article-title":"Endothelial pathomechanisms in acute lung injury","volume":"49","author":"Maniatis","year":"2008","journal-title":"Vascul Pharmacol"},{"key":"2026021904152586800_bib4","doi-asserted-by":"crossref","first-page":"1215","DOI":"10.1007\/s001340051340","article-title":"Regional distribution of gas and tissue in acute respiratory distress syndrome: III. 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