{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,8]],"date-time":"2026-03-08T00:03:17Z","timestamp":1772928197091,"version":"3.50.1"},"reference-count":50,"publisher":"Oxford University Press (OUP)","issue":"1","license":[{"start":{"date-parts":[[2011,1,1]],"date-time":"2011-01-01T00:00:00Z","timestamp":1293840000000},"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":[[2011,1,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>Acute lung injury (ALI) and mechanical ventilator-induced lung injury (VILI), major causes of acute respiratory failure with elevated morbidity and mortality, are characterized by significant pulmonary inflammation and alveolar\/vascular barrier dysfunction. Previous studies highlighted the role of the non\u2013muscle myosin light chain kinase isoform (nmMLCK) as an essential element of the inflammatory response, with variants in the MYLK gene that contribute to ALI susceptibility. To define nmMLCK involvement further in acute inflammatory syndromes, we used two murine models of inflammatory lung injury, induced by either an intratracheal administration of lipopolysaccharide (LPS model) or mechanical ventilation with increased tidal volumes (the VILI model). Intravenous delivery of the membrane-permeant MLC kinase peptide inhibitor, PIK, produced a dose-dependent attenuation of both LPS-induced lung inflammation and VILI (\u223c50% reductions in alveolar\/vascular permeability and leukocyte influx). Intravenous injections of nmMLCK silencing RNA, either directly or as cargo within angiotensin-converting enzyme (ACE) antibody\u2013conjugated liposomes (to target the pulmonary vasculature selectively), decreased nmMLCK lung expression (\u223c70% reduction) and significantly attenuated LPS-induced and VILI-induced lung inflammation (\u223c40% reduction in bronchoalveolar lavage protein). Compared with wild-type mice, nmMLCK knockout mice were significantly protected from VILI, with significant reductions in VILI-induced gene expression in biological pathways such as nrf2-mediated oxidative stress, coagulation, p53-signaling, leukocyte extravasation, and IL-6\u2013signaling. These studies validate nmMLCK as an attractive target for ameliorating the adverse effects of dysregulated lung inflammation.<\/jats:p>","DOI":"10.1165\/rcmb.2009-0197oc","type":"journal-article","created":{"date-parts":[[2010,2,5]],"date-time":"2010-02-05T21:57:30Z","timestamp":1265407050000},"page":"40-52","source":"Crossref","is-referenced-by-count":74,"title":["Non\u2013Muscle Myosin Light Chain Kinase Isoform Is a Viable Molecular Target in Acute Inflammatory Lung Injury"],"prefix":"10.1093","volume":"44","author":[{"given":"Tamara","family":"Mirzapoiazova","sequence":"first","affiliation":[{"name":"Department of Medicine, University of Chicago"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jaideep","family":"Moitra","sequence":"additional","affiliation":[{"name":"Department of Medicine, University of Chicago"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Liliana","family":"Moreno-Vinasco","sequence":"additional","affiliation":[{"name":"Section of Pulmonary, Critical Care, Sleep, and Allergy, University of Illinois at Chicago"},{"name":"Institute for Personalized and Respiratory Medicine, University of Illinois at Chicago, Chicago Illinois"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Saad","family":"Sammani","sequence":"additional","affiliation":[{"name":"Section of Pulmonary, Critical Care, Sleep, and Allergy, University of Illinois at Chicago"},{"name":"Institute for Personalized and Respiratory Medicine, University of Illinois at Chicago, Chicago Illinois"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jerry R.","family":"Turner","sequence":"additional","affiliation":[{"name":"Department of Pathology"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Eddie T.","family":"Chiang","sequence":"additional","affiliation":[{"name":"Section of Pulmonary, Critical Care, Sleep, and Allergy, University of Illinois at Chicago"},{"name":"Institute for Personalized and Respiratory Medicine, University of Illinois at Chicago, Chicago Illinois"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Carrie","family":"Evenoski","sequence":"additional","affiliation":[{"name":"Section of Pulmonary, Critical Care, Sleep, and Allergy, University of Illinois at Chicago"},{"name":"Institute for Personalized and Respiratory Medicine, University of Illinois at Chicago, Chicago Illinois"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ting","family":"Wang","sequence":"additional","affiliation":[{"name":"Section of Pulmonary, Critical Care, Sleep, and Allergy, University of Illinois at Chicago"},{"name":"Institute for Personalized and Respiratory Medicine, University of Illinois at Chicago, Chicago Illinois"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Patrick A.","family":"Singleton","sequence":"additional","affiliation":[{"name":"Section of Pulmonary, Critical Care, Sleep, and Allergy, University of Illinois at Chicago"},{"name":"Institute for Personalized and Respiratory Medicine, University of Illinois at Chicago, Chicago Illinois"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yong","family":"Huang","sequence":"additional","affiliation":[{"name":"Department of Medicine, University of Chicago"},{"name":"Section of Genetic Medicine, University of Chicago"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yves A.","family":"Lussier","sequence":"additional","affiliation":[{"name":"Department of Medicine, University of Chicago"},{"name":"Section of Genetic Medicine, University of Chicago"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"D. 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