Abstract
Hyperoxia-induced lung injury (HALI) is one of the major contributor to the development of bronchopulmonary dysplasia (BPD), a devastating lung disease in premature infants, the mechanisms of which are not fully characterized. Here we report that the triggering receptor expressed on myeloid cells 1 (TREM-1) is upregulated in hyperoxia exposed neonatal mice lungs as well as in human neonatal lungs with respiratory distress syndrome (RDS) and BPD as an adaptive response to survive hyperoxia. Inhibition of TREM-1 function using siRNA approach or deletion of TREM-1 gene in mice showed increased alveolar damage and mortality of hyperoxia-exposed neonatal mice. The treatment of hyperoxia-exposed neonatal mice with agonistic TREM-1 antibody resulted in decreased lung inflammation, increased alveolarization and was associated with decreased necroptosis regulating protein receptor-interacting protein kinase 3 (RIPK3). Mechanistically, we show that TREM-1 alleviates pulmonary alveolar injury and inflammation through down regulating RIPK3 mediated necroptosis in hyperoxia-exposed neonatal mice. These data show that that activating TREM-1, enhancing angiopoietin 1 signaling or blocking RIPK3 mediated necroptosis pathway may act as new therapeutic interventions to control adverse effects of hyperoxia on the development of BPD.
Footnotes
Cite this article as: European Respiratory Journal 2018 52: Suppl. 62, PA1382.
This is an ERS International Congress abstract. No full-text version is available. Further material to accompany this abstract may be available at www.ers-education.org (ERS member access only).
- Copyright ©the authors 2018