TREM-1 Attenuates RIPK3-mediated Necroptosis in Hyperoxia-induced Lung Injury in Neonatal Mice
Authors: Dilip Shah
Sture Andersson
Pragnya Das
Mansoor Ali Syed
Gloria Pryhuber
Vineet Bhandari
Journal: American Journal of Respiratory Cell and Molecular Biology (2019)
Discipline: BIOLOGY & BIOCHEMISTRY
Keywords: NLRP3 inflammasome; TREM-1; bronchopulmonary dysplasia; hyperoxia-induced lung injury; necroptosis.
Affiliations: 1 Drexel University College of Medicine, Philadelphia, Pennsylvania., 2 Children's Hospital, University of Helsinki and Helsinki University Hospital, Helsinki, Finland; and., 3 Department of Pediatrics, University of Rochester School of Medicine and Dentistry, Rochester, New York.

Abstract:  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. 

Retracted: Yes

PubPeer comments:
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 2021 retraction. https: www.atsjournals.org doi full 10.1165 rcmb.v64retraction7 This article (1) has been retracted by its authors. Anomalies were discovered in the images of u03b2-actin blots in Figure 6B, GAPDH in Figures 5I and 5J, and the photomicrographs in Figures 2M and the online supplement Figure E6. The authors acknowledge that the above anomalies compromise the scientific integrity of the paper. All the authors have agreed to the decision to retract this paper; they apologize to the Journal and its readers. Reference. Syed MA, Shah D, Das P, Andersson S, Pryhuber G, Bhandari V. TREM-1 attenuates RIPK3-mediated necroptosis in hyperoxia-induced lung injury in neonatal mice. Am J Respir Cell Mol Biol 2019;60:308u2013322. , 
 https: retractionwatch.com 2022 02 08 philadelphia-area-lung-researcher-up-to-six-retractions ,