{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,10]],"date-time":"2026-10-10T04:43:45Z","timestamp":1791607425987,"version":"4.3.4"},"reference-count":175,"publisher":"MDPI AG","issue":"20","license":[{"start":{"date-parts":[[2022,10,21]],"date-time":"2022-10-21T00:00:00Z","timestamp":1666310400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100000057","name":"NIGMS","doi-asserted-by":"publisher","award":["GM130463"],"award-info":[{"award-number":["GM130463"]}],"id":[{"id":"10.13039\/100000057","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000057","name":"NIGMS","doi-asserted-by":"publisher","award":["HL148695"],"award-info":[{"award-number":["HL148695"]}],"id":[{"id":"10.13039\/100000057","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000057","name":"NIGMS","doi-asserted-by":"publisher","award":["HL130870"],"award-info":[{"award-number":["HL130870"]}],"id":[{"id":"10.13039\/100000057","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000057","name":"NIGMS","doi-asserted-by":"publisher","award":["P30 ES001247"],"award-info":[{"award-number":["P30 ES001247"]}],"id":[{"id":"10.13039\/100000057","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000057","name":"NIGMS","doi-asserted-by":"publisher","award":["ES007026"],"award-info":[{"award-number":["ES007026"]}],"id":[{"id":"10.13039\/100000057","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000050","name":"NHLBI","doi-asserted-by":"publisher","award":["GM130463"],"award-info":[{"award-number":["GM130463"]}],"id":[{"id":"10.13039\/100000050","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000050","name":"NHLBI","doi-asserted-by":"publisher","award":["HL148695"],"award-info":[{"award-number":["HL148695"]}],"id":[{"id":"10.13039\/100000050","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000050","name":"NHLBI","doi-asserted-by":"publisher","award":["HL130870"],"award-info":[{"award-number":["HL130870"]}],"id":[{"id":"10.13039\/100000050","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000050","name":"NHLBI","doi-asserted-by":"publisher","award":["P30 ES001247"],"award-info":[{"award-number":["P30 ES001247"]}],"id":[{"id":"10.13039\/100000050","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000050","name":"NHLBI","doi-asserted-by":"publisher","award":["ES007026"],"award-info":[{"award-number":["ES007026"]}],"id":[{"id":"10.13039\/100000050","id-type":"DOI","asserted-by":"publisher"}]},{"name":"NIH Center","award":["GM130463"],"award-info":[{"award-number":["GM130463"]}]},{"name":"NIH Center","award":["HL148695"],"award-info":[{"award-number":["HL148695"]}]},{"name":"NIH Center","award":["HL130870"],"award-info":[{"award-number":["HL130870"]}]},{"name":"NIH Center","award":["P30 ES001247"],"award-info":[{"award-number":["P30 ES001247"]}]},{"name":"NIH Center","award":["ES007026"],"award-info":[{"award-number":["ES007026"]}]},{"name":"T32 training","award":["GM130463"],"award-info":[{"award-number":["GM130463"]}]},{"name":"T32 training","award":["HL148695"],"award-info":[{"award-number":["HL148695"]}]},{"name":"T32 training","award":["HL130870"],"award-info":[{"award-number":["HL130870"]}]},{"name":"T32 training","award":["P30 ES001247"],"award-info":[{"award-number":["P30 ES001247"]}]},{"name":"T32 training","award":["ES007026"],"award-info":[{"award-number":["ES007026"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Cells"],"abstract":"<jats:p>Acute lung injury\/acute respiratory distress syndrome (ALI\/ARDS) is a devastating disease that can be caused by a variety of conditions including pneumonia, sepsis, trauma, and most recently, COVID-19. Although our understanding of the mechanisms of ALI\/ARDS pathogenesis and resolution has considerably increased in recent years, the mortality rate remains unacceptably high (~40%), primarily due to the lack of effective therapies for ALI\/ARDS. Dysregulated inflammation, as characterized by massive infiltration of polymorphonuclear leukocytes (PMNs) into the airspace and the associated damage of the capillary-alveolar barrier leading to pulmonary edema and hypoxemia, is a major hallmark of ALI\/ARDS. Endothelial cells (ECs), the inner lining of blood vessels, are important cellular orchestrators of PMN infiltration in the lung. Nuclear factor-kappa B (NF-\u03baB) plays an essential role in rendering the endothelium permissive for PMN adhesion and transmigration to reach the inflammatory site. Thus, targeting NF-\u03baB in the endothelium provides an attractive approach to mitigate PMN-mediated vascular injury, not only in ALI\/ARDS, but in other inflammatory diseases as well in which EC dysfunction is a major pathogenic mechanism. This review discusses the role and regulation of NF-\u03baB in the context of EC inflammation and evaluates the potential and problems of targeting it as a therapy for ALI\/ARDS.<\/jats:p>","DOI":"10.3390\/cells11203317","type":"journal-article","created":{"date-parts":[[2022,10,23]],"date-time":"2022-10-23T20:43:50Z","timestamp":1666557830000},"page":"3317","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":157,"title":["Therapeutic Targeting of NF-\u03baB in Acute Lung Injury: A Double-Edged Sword"],"prefix":"10.3390","volume":"11","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-6018-1307","authenticated-orcid":false,"given":"Michelle Warren","family":"Millar","sequence":"first","affiliation":[{"name":"Department of Pediatrics (Neonatology), Lung Biology and Disease Program, University of Rochester School of Medicine and Dentistry, Rochester, NY 14642, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fabeha","family":"Fazal","sequence":"additional","affiliation":[{"name":"Department of Pediatrics (Neonatology), Lung Biology and Disease Program, University of Rochester School of Medicine and Dentistry, Rochester, NY 14642, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Arshad","family":"Rahman","sequence":"additional","affiliation":[{"name":"Department of Pediatrics (Neonatology), Lung Biology and Disease Program, University of Rochester School of Medicine and Dentistry, Rochester, NY 14642, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2022,10,21]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"18","DOI":"10.1038\/s41572-019-0069-0","article-title":"Acute respiratory distress syndrome","volume":"5","author":"Matthay","year":"2019","journal-title":"Nat. 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