{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,28]],"date-time":"2026-09-28T17:09:21Z","timestamp":1790615361316,"version":"4.1.0"},"reference-count":37,"publisher":"Wiley","issue":"16","license":[{"start":{"date-parts":[[2025,8,23]],"date-time":"2025-08-23T00:00:00Z","timestamp":1755907200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001659","name":"Deutsche Forschungsgemeinschaft","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100001659","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["faseb.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["The FASEB Journal"],"published-print":{"date-parts":[[2025,8,31]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:p>\n                    Acute respiratory distress syndrome (ARDS) is characterized by excessive neutrophil\u2010driven inflammation and remains a leading cause of mortality in critical care. Leukotriene\u2010modifying agents, such as montelukast (a CysLTR1 antagonist) and zileuton (a 5\u2010lipoxygenase inhibitor), are approved for chronic inflammatory lung diseases, but their role in ARDS is unclear. We investigated the effects of montelukast and zileuton in a murine model of lipopolysaccharide (LPS)\u2010induced ARDS, supported by in\u00a0vitro assays using human neutrophils. Mice were treated with either drug 1\u2009h post\u2010injury. Neutrophil recruitment, cytokine release, and inflammatory signaling were assessed by immunohistochemistry, flow cytometry, ELISA, and qPCR. Neutrophil chemotaxis and signaling responses were evaluated in\u00a0vitro. Both montelukast and zileuton significantly reduced neutrophil infiltration into lung tissue and bronchoalveolar lavage fluid (\n                    <jats:italic>p<\/jats:italic>\n                    \u2009&lt;\u20090.01), suppressed expression of adhesion molecules (PSGL\u20101, L\u2010selectin, LFA\u20101), and decreased levels of TNF\u2010\u03b1, CXCL2, IL\u20101\u03b2, and IL\u20106 in BAL fluid (\n                    <jats:italic>p<\/jats:italic>\n                    \u2009&lt;\u20090.05). In\u00a0vitro, both drugs impaired neutrophil chemotaxis and reduced CysLTR1 and ERK1\/2 expression following inflammatory stimulation. These findings indicate that leukotriene pathway inhibition limits neutrophil recruitment and activation in ARDS by modulating receptor expression and ERK1\/2 signaling. Montelukast and zileuton may offer a targeted strategy to attenuate hyperinflammation in ARDS.\n                  <\/jats:p>","DOI":"10.1096\/fj.202501684r","type":"journal-article","created":{"date-parts":[[2025,8,23]],"date-time":"2025-08-23T10:03:33Z","timestamp":1755943413000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":3,"title":["Modulation of Neutrophil Recruitment and Inflammatory Signaling in Acute Respiratory Distress Syndrome by Leukotriene Inhibitors Montelukast and Zileuton"],"prefix":"10.1096","volume":"39","author":[{"given":"Anna","family":"Biedritzky","sequence":"first","affiliation":[{"name":"Department of Anesthesiology and Intensive Care Medicine University Hospital of Tuebingen  T\u00fcbingen Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yi","family":"Zhang","sequence":"additional","affiliation":[{"name":"Department of Anesthesiology Shenzhen Hospital of Southern Medical University  Shenzhen Guangdong China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anika","family":"Fuhr","sequence":"additional","affiliation":[{"name":"Department of Anesthesiology and Intensive Care Medicine University Hospital of Tuebingen  T\u00fcbingen Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Carolin","family":"Kleinmaier","sequence":"additional","affiliation":[{"name":"Department of Anesthesiology and Intensive Care Medicine University Hospital of Tuebingen  T\u00fcbingen Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jutta","family":"Gamper\u2010Tsigaras","sequence":"additional","affiliation":[{"name":"Department of Anesthesiology and Intensive Care Medicine University Hospital of Tuebingen  T\u00fcbingen Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ka\u2010Lin","family":"Heck\u2010Swain","sequence":"additional","affiliation":[{"name":"Department of Anesthesiology and Intensive Care Medicine University Hospital of Tuebingen  T\u00fcbingen Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kristian\u2010Christos","family":"Ngamsri","sequence":"additional","affiliation":[{"name":"Department of Anesthesiology and Intensive Care Medicine University Hospital of Tuebingen  T\u00fcbingen Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Franziska","family":"Konrad","sequence":"additional","affiliation":[{"name":"Klinik f\u00fcr An\u00e4sthesiologie Orthop\u00e4dische Klinik Markgr\u00f6ningen  Markgr\u00f6ningen Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5002-1286","authenticated-orcid":false,"given":"Michael","family":"Koeppen","sequence":"additional","affiliation":[{"name":"Department of Anesthesiology and Intensive Care Medicine University Hospital of Tuebingen  T\u00fcbingen 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