{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,18]],"date-time":"2026-08-18T01:58:30Z","timestamp":1787018310726,"version":"build-2736575974"},"reference-count":46,"publisher":"Oxford University Press (OUP)","issue":"3","license":[{"start":{"date-parts":[[2019,3,1]],"date-time":"2019-03-01T00:00:00Z","timestamp":1551398400000},"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":[[2019,3,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>RETRACTED: Hyperoxia-induced injury to the developing lung, impaired alveolarization, and dysregulated vascularization are critical factors in the pathogenesis of bronchopulmonary dysplasia (BPD); however, mechanisms for hyperoxia-induced development of BPD are not fully known. In this study, we show that TREM-1 (triggering receptor expressed on myeloid cells 1) is upregulated in hyperoxia-exposed neonatal murine lungs as well as in tracheal aspirates and lungs of human neonates with respiratory distress syndrome and BPD as an adaptive response to survival in hyperoxia. Inhibition of TREM-1 function using an siRNA approach or deletion of the Trem1 gene in mice showed enhanced lung inflammation, alveolar damage, and mortality of hyperoxia-exposed neonatal mice. The treatment of hyperoxia-exposed neonatal mice with agonistic TREM-1 antibody decreased lung inflammation, improved alveolarization, and was associated with diminished necroptosis-regulating protein RIPK3 (receptor-interacting protein kinase 3). Mechanistically, we show that TREM-1 activation alleviates lung inflammation and improves alveolarization through downregulating RIPK3-mediated necroptosis and NLRP3 (nucleotide-binding oligomerization domain-like receptor containing pyrin domain 3) inflammasome activation in hyperoxia-exposed neonatal mice. These data show that activating TREM-1, enhancing angiopoietin 1 signaling, or blocking the RIPK3-mediated necroptosis pathway may be used in new therapeutic interventions to control adverse effects of hyperoxia in the development of BPD.<\/jats:p>","DOI":"10.1165\/rcmb.2018-0219oc","type":"journal-article","created":{"date-parts":[[2018,10,3]],"date-time":"2018-10-03T14:48:41Z","timestamp":1538578121000},"page":"308-322","source":"Crossref","is-referenced-by-count":20,"title":["TREM-1 Attenuates RIPK3-mediated Necroptosis in Hyperoxia-induced Lung Injury in Neonatal Mice"],"prefix":"10.1093","volume":"60","author":[{"given":"Mansoor Ali","family":"Syed","sequence":"first","affiliation":[{"name":"Drexel University College of Medicine, Philadelphia, Pennsylvania"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4248-5611","authenticated-orcid":false,"given":"Dilip","family":"Shah","sequence":"additional","affiliation":[{"name":"Drexel University College of Medicine, Philadelphia, Pennsylvania"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pragnya","family":"Das","sequence":"additional","affiliation":[{"name":"Drexel University College of Medicine, Philadelphia, Pennsylvania"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sture","family":"Andersson","sequence":"additional","affiliation":[{"name":"Children\u2019s Hospital, University of Helsinki and Helsinki University Hospital, Helsinki, Finland; and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gloria","family":"Pryhuber","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, University of Rochester School of Medicine and Dentistry, Rochester, New York"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4900-6636","authenticated-orcid":false,"given":"Vineet","family":"Bhandari","sequence":"additional","affiliation":[{"name":"Drexel University College of Medicine, Philadelphia, Pennsylvania"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2019,3,1]]},"reference":[{"key":"2026012222063352900_bib1","doi-asserted-by":"crossref","first-page":"223","DOI":"10.1016\/j.siny.2010.03.009","article-title":"Hyperoxia-derived lung damage in preterm infants","volume":"15","author":"Bhandari","year":"2010","journal-title":"Semin Fetal Neonatal Med"},{"key":"2026012222063352900_bib2","doi-asserted-by":"crossref","first-page":"3","DOI":"10.1007\/978-3-319-28486-6_1","article-title":"Hyperoxia in the pathogenesis of bronchopulmonary dysplasia","volume-title":"Bronchopulmonary dysplasia","author":"Harijith","year":"2016"},{"key":"2026012222063352900_bib3","doi-asserted-by":"crossref","first-page":"8977","DOI":"10.1038\/ncomms9977","article-title":"The NLRP3 inflammasome is critically involved in the development of bronchopulmonary dysplasia","volume":"6","author":"Liao","year":"2015","journal-title":"Nat Commun"},{"key":"2026012222063352900_bib4","doi-asserted-by":"crossref","first-page":"270","DOI":"10.1165\/rcmb.2013-0087OC","article-title":"The NLRP3 inflammasome is required for the development of hypoxemia in LPS\/mechanical ventilation acute lung injury","volume":"50","author":"Jones","year":"2014","journal-title":"Am J Respir Cell Mol Biol"},{"key":"2026012222063352900_bib5","doi-asserted-by":"crossref","first-page":"145","DOI":"10.1002\/path.4124","article-title":"Danger-associated molecular patterns (DAMPs) in acute lung injury","volume":"229","author":"Tolle","year":"2013","journal-title":"J Pathol"},{"key":"2026012222063352900_bib6","doi-asserted-by":"crossref","first-page":"445","DOI":"10.1038\/nri1106","article-title":"TREMs in the immune system and beyond","volume":"3","author":"Colonna","year":"2003","journal-title":"Nat Rev Immunol"},{"key":"2026012222063352900_bib7","doi-asserted-by":"crossref","first-page":"701","DOI":"10.1016\/j.imbio.2008.07.008","article-title":"From expression to signaling: roles of TREM-1 and TREM-2 in innate immunity and bacterial infection","volume":"213","author":"Sharif","year":"2008","journal-title":"Immunobiology"},{"key":"2026012222063352900_bib8","doi-asserted-by":"crossref","first-page":"138","DOI":"10.1172\/JCI64181","article-title":"Transepithelial migration of neutrophils into the lung requires TREM-1","volume":"123","author":"Klesney-Tait","year":"2013","journal-title":"J Clin Invest"},{"key":"2026012222063352900_bib9","doi-asserted-by":"crossref","first-page":"1464","DOI":"10.1128\/MCB.24.4.1464-1469.2004","article-title":"Kinase RIP3 is dispensable for normal NF-\u03baBs, signaling by the B-cell and T-cell receptors, tumor necrosis factor receptor 1, and Toll-like receptors 2 and 4","volume":"24","author":"Newton","year":"2004","journal-title":"Mol Cell Biol"},{"key":"2026012222063352900_bib10","doi-asserted-by":"crossref","first-page":"1173","DOI":"10.1038\/s41467-017-01349-y","article-title":"Hyperoxia causes miR-34a-mediated injury via angiopoietin-1 in neonatal lungs","volume":"8","author":"Syed","year":"2017","journal-title":"Nat Commun"},{"key":"2026012222063352900_bib11","doi-asserted-by":"crossref","first-page":"722","DOI":"10.1165\/rcmb.2015-0349OC","article-title":"Inhibition of regulatory-associated protein of mechanistic target of rapamycin prevents hyperoxia-induced lung injury by enhancing autophagy and reducing apoptosis in neonatal mice","volume":"55","author":"Sureshbabu","year":"2016","journal-title":"Am J Respir Cell Mol Biol"},{"key":"2026012222063352900_bib12","doi-asserted-by":"crossref","first-page":"L152","DOI":"10.1152\/ajplung.00229.2013","article-title":"Extracellular ATP mediates the late phase of neutrophil recruitment to the lung in murine models of acute lung injury","volume":"306","author":"Shah","year":"2014","journal-title":"Am J Physiol Lung Cell Mol Physiol"},{"key":"2026012222063352900_bib13","doi-asserted-by":"crossref","first-page":"29642","DOI":"10.1074\/jbc.M115.690784","article-title":"C1q deficiency promotes pulmonary vascular inflammation and enhances the susceptibility of the lung endothelium to injury","volume":"290","author":"Shah","year":"2015","journal-title":"J Biol Chem"},{"key":"2026012222063352900_bib14","doi-asserted-by":"crossref","first-page":"e60560","DOI":"10.1371\/journal.pone.0060560","article-title":"A critical regulatory role for macrophage migration inhibitory factor in hyperoxia-induced injury in the developing murine lung","volume":"8","author":"Sun","year":"2013","journal-title":"PLoS One"},{"key":"2026012222063352900_bib15","doi-asserted-by":"crossref","first-page":"668","DOI":"10.1165\/rcmb.2011-0074OC","article-title":"Increased hyperoxia-induced lung injury in nitric oxide synthase 2 null mice is mediated via angiopoietin 2","volume":"46","author":"Bhandari","year":"2012","journal-title":"Am J Respir Cell Mol Biol"},{"key":"2026012222063352900_bib16","doi-asserted-by":"crossref","first-page":"L936","DOI":"10.1152\/ajplung.00159.2014","article-title":"Animal models of bronchopulmonary dysplasia: the term mouse models","volume":"307","author":"Berger","year":"2014","journal-title":"Am J Physiol Lung Cell Mol Physiol"},{"key":"2026012222063352900_bib17","doi-asserted-by":"crossref","first-page":"2027","DOI":"10.4049\/jimmunol.0803862","article-title":"TREM-1 activation alters the dynamics of pulmonary IRAK-M expression in vivo and improves host defense during pneumococcal pneumonia","volume":"183","author":"Lagler","year":"2009","journal-title":"J Immunol"},{"key":"2026012222063352900_bib18","doi-asserted-by":"crossref","first-page":"3293","DOI":"10.1128\/IAI.00440-15","article-title":"TREM-1 signaling promotes host defense during the early stage of infection with highly pathogenic Streptococcus suis","volume":"83","author":"Yang","year":"2015","journal-title":"Infect Immun"},{"key":"2026012222063352900_bib19","doi-asserted-by":"crossref","first-page":"15118","DOI":"10.1074\/jbc.M113.536490","article-title":"Triggering receptor expressed on myeloid cells 1 (TREM-1)-mediated Bcl-2 induction prolongs macrophage survival","volume":"289","author":"Yuan","year":"2014","journal-title":"J Biol Chem"},{"key":"2026012222063352900_bib20","doi-asserted-by":"crossref","first-page":"145","DOI":"10.1016\/j.yexmp.2007.11.004","article-title":"Regulation of TREM expression in hepatic macrophages and endothelial cells during acute endotoxemia","volume":"84","author":"Chen","year":"2008","journal-title":"Exp Mol Pathol"},{"key":"2026012222063352900_bib21","doi-asserted-by":"crossref","first-page":"280","DOI":"10.1159\/000450918","article-title":"Inhibition of Rac1 signaling downregulates inflammasome activation and attenuates lung injury in neonatal rats exposed to hyperoxia","volume":"111","author":"Hummler","year":"2017","journal-title":"Neonatology"},{"key":"2026012222063352900_bib22","doi-asserted-by":"crossref","first-page":"610","DOI":"10.1038\/jp.2010.16","article-title":"High-mobility group box-1 protein in tracheal aspirates from premature infants: relationship with bronchopulmonary dysplasia and steroid therapy","volume":"30","author":"Aghai","year":"2010","journal-title":"J Perinatol"},{"key":"2026012222063352900_bib23","doi-asserted-by":"crossref","first-page":"6282","DOI":"10.1038\/ncomms7282","article-title":"RIPK3 promotes cell death and NLRP3 inflammasome activation in the absence of MLKL","volume":"6","author":"Lawlor","year":"2015","journal-title":"Nat Commun"},{"key":"2026012222063352900_bib24","doi-asserted-by":"crossref","first-page":"27","DOI":"10.1016\/j.immuni.2012.09.015","article-title":"Caspase-8 blocks kinase RIPK3-mediated activation of the NLRP3 inflammasome","volume":"38","author":"Kang","year":"2013","journal-title":"Immunity"},{"key":"2026012222063352900_bib25","doi-asserted-by":"crossref","first-page":"5974","DOI":"10.4049\/jimmunol.1400368","article-title":"Critical role for the NLRP3 inflammasome during acute lung injury","volume":"192","author":"Grailer","year":"2014","journal-title":"J Immunol"},{"key":"2026012222063352900_bib26","doi-asserted-by":"crossref","first-page":"1602","DOI":"10.1016\/j.bbrc.2016.08.163","article-title":"Necrostatin-1 protects against oleic acid-induced acute respiratory distress syndrome in rats","volume":"478","author":"Pan","year":"2016","journal-title":"Biochem Biophys Res Commun"},{"key":"2026012222063352900_bib27","doi-asserted-by":"crossref","first-page":"e0155723","DOI":"10.1371\/journal.pone.0155723","article-title":"Receptor interacting protein 3-mediated necroptosis promotes lipopolysaccharide-induced inflammation and acute respiratory distress syndrome in mice","volume":"11","author":"Wang","year":"2016","journal-title":"PLoS One"},{"key":"2026012222063352900_bib28","doi-asserted-by":"crossref","first-page":"3987","DOI":"10.1172\/JCI74985","article-title":"Mitophagy-dependent necroptosis contributes to the pathogenesis of COPD","volume":"124","author":"Mizumura","year":"2014","journal-title":"J Clin Invest"},{"key":"2026012222063352900_bib29","doi-asserted-by":"crossref","first-page":"407","DOI":"10.1016\/j.resinv.2016.03.008","article-title":"The role of necroptosis in pulmonary diseases","volume":"54","author":"Mizumura","year":"2016","journal-title":"Respir Investig"},{"key":"2026012222063352900_bib30","doi-asserted-by":"crossref","first-page":"908","DOI":"10.1016\/j.immuni.2011.09.020","article-title":"RIP kinase-dependent necrosis drives lethal systemic inflammatory response syndrome","volume":"35","author":"Duprez","year":"2011","journal-title":"Immunity"},{"key":"2026012222063352900_bib31","doi-asserted-by":"crossref","first-page":"e1005337","DOI":"10.1371\/journal.ppat.1005337","article-title":"Pore-forming toxins induce macrophage necroptosis during acute bacterial pneumonia","volume":"11","author":"Gonz\u00e1lez-Juarbe","year":"2015","journal-title":"PLoS Pathog"},{"key":"2026012222063352900_bib32","doi-asserted-by":"crossref","first-page":"1049","DOI":"10.4161\/cc.6.9.4229","article-title":"The role of angiopoietin 2 in hyperoxia-induced acute lung injury","volume":"6","author":"Bhandari","year":"2007","journal-title":"Cell Cycle"},{"key":"2026012222063352900_bib33","doi-asserted-by":"crossref","first-page":"1286","DOI":"10.1038\/nm1494","article-title":"Hyperoxia causes angiopoietin 2-mediated acute lung injury and necrotic cell death","volume":"12","author":"Bhandari","year":"2006","journal-title":"Nat Med"},{"key":"2026012222063352900_bib34","doi-asserted-by":"crossref","first-page":"1103","DOI":"10.1038\/35074114","article-title":"TREM-1 amplifies inflammation and is a crucial mediator of septic shock","volume":"410","author":"Bouchon","year":"2001","journal-title":"Nature"},{"key":"2026012222063352900_bib35","doi-asserted-by":"crossref","first-page":"530","DOI":"10.1038\/87846","article-title":"TREM-1: a new regulator of innate immunity in sepsis syndrome","volume":"7","author":"Nathan","year":"2001","journal-title":"Nat Med"},{"key":"2026012222063352900_bib36","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1097\/DCC.0b013e31823a5298","article-title":"Triggering receptor expressed on myeloid cells type 1 as a potential therapeutic target in sepsis","volume":"31","author":"Palazzo","year":"2012","journal-title":"Dimens Crit Care Nurs"},{"key":"2026012222063352900_bib37","doi-asserted-by":"crossref","first-page":"39473","DOI":"10.1038\/srep39473","article-title":"Blocking triggering receptor expressed on myeloid cells-1 attenuates lipopolysaccharide-induced acute lung injury via inhibiting NLRP3 inflammasome activation","volume":"6","author":"Liu","year":"2016","journal-title":"Sci Rep"},{"key":"2026012222063352900_bib38","doi-asserted-by":"crossref","first-page":"907","DOI":"10.1093\/cvr\/cvy018","article-title":"Targeted endothelial gene deletion of triggering receptor expressed on myeloid cells-1 protects mice during septic shock","volume":"114","author":"Jolly","year":"2018","journal-title":"Cardiovasc Res"},{"key":"2026012222063352900_bib39","first-page":"106","article-title":"Timing and expression of the angiopoietin-1-Tie-2 pathway in murine lung development and congenital diaphragmatic hernia","volume":"6","author":"Grzenda","year":"2013","journal-title":"Dis Model Mech"},{"key":"2026012222063352900_bib40","doi-asserted-by":"crossref","first-page":"e82088","DOI":"10.1371\/journal.pone.0082088","article-title":"Tie2 signaling cooperates with TNF to promote the pro-inflammatory activation of human macrophages independently of macrophage functional phenotype","volume":"9","author":"Garc\u00eda","year":"2014","journal-title":"PLoS One"},{"key":"2026012222063352900_bib41","doi-asserted-by":"crossref","first-page":"550","DOI":"10.1007\/s10059-013-0088-8","article-title":"Angiopoietin-1 elicits pro-inflammatory responses in monocytes and differentiating macrophages","volume":"35","author":"Seok","year":"2013","journal-title":"Mol Cells"},{"key":"2026012222063352900_bib42","doi-asserted-by":"crossref","first-page":"209","DOI":"10.1016\/j.immuni.2013.02.003","article-title":"Necroptosis: the release of damage-associated molecular patterns and its physiological relevance","volume":"38","author":"Kaczmarek","year":"2013","journal-title":"Immunity"},{"key":"2026012222063352900_bib43","doi-asserted-by":"crossref","first-page":"51","DOI":"10.1038\/nri3561","article-title":"Concepts of tissue injury and cell death in inflammation: a historical perspective","volume":"14","author":"Wallach","year":"2014","journal-title":"Nat Rev Immunol"},{"key":"2026012222063352900_bib44","doi-asserted-by":"crossref","first-page":"159","DOI":"10.1089\/jir.2015.0080","article-title":"High-mobility group box-1 protein disrupts alveolar elastogenesis of hyperoxia-injured newborn lungs","volume":"36","author":"Yu","year":"2016","journal-title":"J Interferon Cytokine Res"},{"key":"2026012222063352900_bib45","doi-asserted-by":"crossref","first-page":"E961","DOI":"10.1073\/pnas.1613305114","article-title":"Active MLKL triggers the NLRP3 inflammasome in a cell-intrinsic manner","volume":"114","author":"Conos","year":"2017","journal-title":"Proc Natl Acad Sci USA"},{"key":"2026012222063352900_bib46","doi-asserted-by":"crossref","first-page":"76","DOI":"10.1038\/cdd.2015.70","article-title":"Characterization of RIPK3-mediated phosphorylation of the activation loop of MLKL during necroptosis","volume":"23","author":"Rodriguez","year":"2016","journal-title":"Cell Death Differ"}],"updated-by":[{"DOI":"10.1165\/rcmb.v64retraction7","type":"retraction","label":"Retraction","source":"retraction-watch","updated":{"date-parts":[[2021,4,1]],"date-time":"2021-04-01T00:00:00Z","timestamp":1617235200000},"record-id":"27071"},{"DOI":"10.1165\/rcmb.v64retraction7","type":"retraction","label":"Retraction","source":"publisher","updated":{"date-parts":[[2021,4,1]],"date-time":"2021-04-01T00:00:00Z","timestamp":1617235200000}}],"container-title":["American Journal of Respiratory Cell and Molecular Biology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/academic.oup.com\/ajrcmb\/article-pdf\/60\/3\/308\/66464978\/ajrcmb_60_3_308.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"https:\/\/academic.oup.com\/ajrcmb\/article-pdf\/60\/3\/308\/66464978\/ajrcmb_60_3_308.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,1,23]],"date-time":"2026-01-23T03:10:13Z","timestamp":1769137813000},"score":1,"resource":{"primary":{"URL":"https:\/\/academic.oup.com\/ajrcmb\/article\/60\/3\/308\/8430344"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2019,3,1]]},"references-count":46,"journal-issue":{"issue":"3","published-online":{"date-parts":[[2019,3,1]]},"published-print":{"date-parts":[[2019,3,1]]}},"URL":"https:\/\/doi.org\/10.1165\/rcmb.2018-0219oc","relation":{},"ISSN":["1044-1549","1535-4989"],"issn-type":[{"value":"1044-1549","type":"print"},{"value":"1535-4989","type":"electronic"}],"subject":[],"published-other":{"date-parts":[[2019,3]]},"published":{"date-parts":[[2019,3,1]]}}}