μ-Opioid receptor signalling via PI3K/Akt pathway ameliorates lipopolysaccharide-induced acute respiratory distress syndrome

Abstract

New Findings: What is the central question of this study? The aim was to investigate the role of μ-opioid receptors in acute respiratory distress syndrome and whether their protective effect is mediated via the PI3K/Akt signalling pathway. What is the main finding and its importance? Our findings show that activation of μ-opioid receptors ameliorates lung injury, and the effects are reversed by the PI3K inhibitor, wortmannin. Abstract: The main pathology of acute respiratory distress syndrome (ARDS) is the accumulation of inflammatory cells in the lung and increased permeability of vascular endothelial cells. The μ-opioid receptor (MOR) is a G-protein-coupled receptor, which stimulates angiogenesis and vascular endothelial cell proliferation. In addition, the MOR inhibits cell apoptosis via the PI3K/Akt signalling pathway. In this study, we aimed to explore the contribution of the MOR in ARDS and whether its effects are mediated via PI3K/Akt signalling. An ARDS model was established by intratracheal instillation of 5 mg kg−1 lipopolysaccharide (LPS). Lung injury was confirmed by Haematoxylin and Eosin staining, lung wet/dry weight ratio, bronchoalveolar lavage fluid protein concentrations, myeloperoxidase activity and vascular cell adhesion molecule 1 expression. Lung inflammation was determined by assessment of interleukin-1β and tumour necrosis factor-α concentrations. The protein level of p-Akt was detected by western blot. Endomorphin-1-activated MORs attenuated LPS-induced lung injury, lung wet/dry weight ratio, bronchoalveolar lavage fluid protein concentrations, myeloperoxidase activity, interleukin-1β and tumour necrosis factor-α levels and vascular cell adhesion molecule 1 expression, and elevated LPS-induced decreased p-Akt expression. However, the protective effect of MOR activation on lung injury was reversed by the PI3K inhibitor, wortmannin. In conclusion, MOR involvement in LPS-induced ARDS is via the PI3K/Akt pathway.