Role of TREM1-Ripk3 axis in hyperoxia induced lung injury in neonates.

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.

Source: European Respiratory Journal - November 19, 2018 Category: Respiratory Medicine Authors: Syed, M. A., Shah, D., Bhandari, V. Tags: Lung and airway developmental biology Source Type: research