The protective effects of glutamine against bronchopulmonary dysplasia are associated with MKP-1/MAPK/cPLA2 signalingmediated NF-kappaB pathway.

Abstract

Glutamine is proven to have potential therapeutic effects on decreasing hyperoxia-induced acute pulmonary injury. The aim of this study is to investigate the effects and mechanism of glutamine on bronchopulmonary dysplasia (BPD) induced by hyperoxia in rat alveolar type II epithelial cells (AECIIs) RLE-6TN. Following hyperoxia induction and glutamine treatment, ROS levels were detected by DCFH-DA assay and TUNEL staining was performed to detect cell apoptosis. The levels of inflammatory indicators and expression of apoptosis-related proteins were detected through ELISA and Western blot, respectively. Besides, the expression of related proteins in mitogen-activated protein kinase phosphatase-1 (MKP-1)/mitogen-activated protein kinases (MAPK)/cytoplasmic phospholipase A2 (cPLA2) signaling was also detected by Western blot. To further analyze the role of MKP-1/MAPK/cPLA2 signaling, MKP-1 was silenced and anisomycin was used to treat cells, respectively. It was shown that glutamine significantly decreased inflammation, oxidative stress and apoptosis in hyperoxia-induced cells while MKP-1 interference and anisomycin were able to reverse these effects, suggesting that the protective effects of glutamine on BPD induced by hypoxia were related to MKP-1/MAPK/cPLA2 signaling. To sum up, glutamine protected against BPD by decreasing inflammation, oxidative stress and apoptosis via MKP-1/MAPK/cPLA2 signaling.