Intratracheal transplantation of mesenchymal stem cells attenuates hyperoxia-induced lung injury by down-regulating, but not direct inhibiting formyl peptide receptor 1 in the newborn mice

Young Eun Kim, Won Soon Park, So Yoon Ahn, Dong Kyung Sung, Yun Sil Chang, Harald Ehrhardt
2018 PLoS ONE  
Formyl peptide receptor 1 (FPR1) has been shown to be a key regulator of inflammation. However, its role in bronchopulmonary dysplasia (BPD) has not been delineated yet. We investigated whether FPR1 plays a pivotal role in regulating lung inflammation and injuries, and whether intratracheally transplanted mesenchymal stem cells (MSCs) attenuate hyperoxic lung inflammation and injuries by down-regulating FPR1. Newborn wild type (WT) or FPR1 knockout (FPR1 -/-) C57/BL6 mice were randomly exposed
more » ... e randomly exposed to 80% oxygen or room air for 14 days. At postnatal day (P) 5, 2×10 5 MSCs were intratracheally transplanted. At P14, mice were sacrificed for histopathological and morphometric analyses. Hyperoxia significantly increased lung neutrophils, macrophages, and TUNEL-positive cells, while impairing alveolarization and angiogenesis, along with a significant increase in FPR1 mRNA levels in WT mice. The hyperoxia-induced lung inflammation and lung injuries were significantly attenuated, with the reduced mRNA level of FPR1, in WT mice with MSC transplantation and in FPR1 -/mice, irrespective of MSCs transplantation. However, only MSC transplantation, but not the FPR1 knockout, significantly attenuated the hyperoxia-induced increase in TUNEL-positive cells. Our findings indicate that FPR1 play a critical role in regulating lung inflammation and injuries in BPD, and MSCs attenuate hyperoxic lung inflammation and injuries, but not apoptosis, with down regulating, but not direct inhibiting FPR1. OPEN ACCESS Citation: Kim YE, Park WS, Ahn SY, Sung DK, Chang YS (2018) Intratracheal transplantation of mesenchymal stem cells attenuates hyperoxiainduced lung injury by down-regulating, but not direct inhibiting formyl peptide receptor 1 in the newborn mice. PLoS ONE 13(10): e0206311.
doi:10.1371/journal.pone.0206311 fatcat:axqgct7nv5fp7bynu6gq5esynm