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Journal article
TREM-1 Attenuates RIPK3-mediated Necroptosis in Hyperoxia-induced Lung Injury in Neonatal Mice
American journal of respiratory cell and molecular biology, v 60(3)
01 Mar 2019
PMID: 30281332
Featured in Collection : UN Sustainable Development Goals @ Drexel
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 Trem 1 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.
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Details
- Title
- TREM-1 Attenuates RIPK3-mediated Necroptosis in Hyperoxia-induced Lung Injury in Neonatal Mice
- Creators
- Mansoor Ali Syed - Drexel UniversityDilip Shah - Drexel UniversityPragnya Das - Drexel UniversitySture Andersson - Helsinki University HospitalGloria Pryhuber - University of RochesterVineet Bhandari - Drexel University
- Publication Details
- American journal of respiratory cell and molecular biology, v 60(3)
- Publisher
- Amer Thoracic Soc
- Number of pages
- 15
- Grant note
- Finnish governmental subsidy for clinical research HL63039 / National Heart, Lung, and Blood Institute from the National Institutes of Health
- Resource Type
- Journal article
- Language
- English
- Academic Unit
- Pediatrics
- Web of Science ID
- WOS:000460047400011
- Scopus ID
- 2-s2.0-85062293255
- Other Identifier
- 991019167555004721
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- Collaboration types
- Domestic collaboration
- International collaboration
- Web of Science research areas
- Biochemistry & Molecular Biology
- Cell Biology
- Respiratory System