{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,10]],"date-time":"2026-10-10T04:43:03Z","timestamp":1791607383546,"version":"4.3.4"},"reference-count":40,"publisher":"Oxford University Press (OUP)","issue":"3","license":[{"start":{"date-parts":[[2018,3,1]],"date-time":"2018-03-01T00:00:00Z","timestamp":1519862400000},"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":[[2018,3,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>Acute lung injury (ALI) is a clinical syndrome characterized by acute respiratory failure and is associated with substantial morbidity and mortality. Rhesus \u03b8-defensin (RTD)-1 is an antimicrobial peptide with immunomodulatory activity. As airway inflammation and neutrophil recruitment and activation are hallmarks of ALI, we evaluated the therapeutic efficacy of RTD-1 in preclinical models of the disease. We investigated the effect of RTD-1 on neutrophil chemotaxis and macrophage-driven pulmonary inflammation with human peripheral neutrophils and LPS-stimulated murine alveolar macrophage (denoted MH-S) cells. Treatment and prophylactic single escalating doses were administered subcutaneously in a well-established murine model of direct endotoxin-induced ALI. We assessed lung injury by histopathology, pulmonary edema, inflammatory cell recruitment, and inflammatory cytokines\/chemokines in the BAL fluid. In vitro studies demonstrated that RTD-1 suppressed CXCL8-induced neutrophil chemotaxis, TNF-mediated neutrophil\u2013endothelial cell adhesion, and proinflammatory cytokine release in activated murine alveolar immortalized macrophages (MH-S) cells. Treatment with RTD-1 significantly inhibited in vivo LPS-induced ALI by reducing pulmonary edema and histopathological changes. Treatment was associated with dose- and time-dependent inhibition of proinflammatory cytokines (TNF, IL-1\u03b2, and IL-6), peroxidase activity, and neutrophil recruitment into the airways. Antiinflammatory effects were demonstrated in animals receiving RTD-1 up to 12 hours after LPS challenge. Notably, subcutaneously administered RTD-1 demonstrates good peptide stability as demonstrated by the long in vivo half-life. Taken together, these studies demonstrate that RTD-1 is efficacious in an experimental model of ALI through inhibition of neutrophil chemotaxis and adhesion, and the attenuation of proinflammatory cytokines and gene expression from alveolar macrophages.<\/jats:p>","DOI":"10.1165\/rcmb.2016-0428oc","type":"journal-article","created":{"date-parts":[[2017,9,27]],"date-time":"2017-09-27T18:44:30Z","timestamp":1506537870000},"page":"310-319","source":"Crossref","is-referenced-by-count":24,"title":["Rhesus \u03b8-Defensin-1 Attenuates Endotoxin-induced Acute Lung Injury by Inhibiting Proinflammatory Cytokines and Neutrophil Recruitment"],"prefix":"10.1093","volume":"58","author":[{"given":"Jordanna G.","family":"Jayne","sequence":"first","affiliation":[{"name":"School of Pharmacy and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Timothy J.","family":"Bensman","sequence":"additional","affiliation":[{"name":"School of Pharmacy and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Justin B.","family":"Schaal","sequence":"additional","affiliation":[{"name":"Keck School of Medicine, University of Southern California, Los Angeles, California; and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"A. Young J.","family":"Park","sequence":"additional","affiliation":[{"name":"School of Pharmacy and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Elza","family":"Kimura","sequence":"additional","affiliation":[{"name":"State University of Maring\u00e1, Maring\u00e1, Paran\u00e1, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dat","family":"Tran","sequence":"additional","affiliation":[{"name":"Keck School of Medicine, University of Southern California, Los Angeles, California; and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michael E.","family":"Selsted","sequence":"additional","affiliation":[{"name":"Keck School of Medicine, University of Southern California, Los Angeles, California; and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3744-3310","authenticated-orcid":false,"given":"Paul M.","family":"Beringer","sequence":"additional","affiliation":[{"name":"School of Pharmacy 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