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.

Opioids for the relief of acute respiratory distress syndrome: Endomorphins are the μ kids on the block!

“…The study by Ji and Wang () complements and extends previous work revealing that μ‐opioid activation is effective in attenuating lung injury in rats via downregulation of the pro‐inflammatory transcription factor nuclear factor‐κB (Zhang, Du, Zhou, Wang, & Li, ), a downstream target of the PI3K/Akt signalling cascade. Together, these studies provide a mechanistic link supporting anti‐inflammatory actions of μ‐opioid receptor activation relevant to pulmonary disease, albeit that specific cell types were not characterized in the study by Ji and Wang ().…”

“…In this issue of Experimental Physiology , Ji and Wang () provide evidence that μ‐opioid receptor activation ameliorates pathophysiological features in an animal model of ARDS. Tracheal instillation of lipopolysaccharide in adult mice evoked pulmonary injury characterized histologically and by evidence of pulmonary oedema and increased protein concentration in the bronchoalveolar lavage fluid, with augmented levels of inflammatory mediators (interleukin‐1β and tumour necrosis factor‐α) and increased myeloperoxidase activity, a surrogate marker of neutrophil infiltration.…”

“…To conclude, the study of Ji and Wang () illustrates that μ‐opioid receptor activation mitigates key pathophysiological traits of bacterially induced lung injury, paving the way for the exploration of their potential application in the treatment of ARDS. Time will tell whether opioid therapy provides for no pain with pulmonary gain.…”

Up-regulation of miR-146b-3p protects septic mice with acute respiratory distress syndrome by inhibiting PI3K/AKT signaling pathway

“…Moreover, AKT is generally recognized as a key factor in PI3K (phosphatidylinositol 3-kinase) /AKT pathway and acts as a crucial role in cell differentiation, proliferation, metabolism, apoptosis, protein synthesis and transcription (Li et al 2015). Previous studies have indicated that ARDS can be treated by the inhibition of PI3K/AKT signaling pathway (Ji and Wang 2019;Li et al 2018b;Yanagi et al 2015;Zheng et al 2018).…”

miR-146b-3p regulates PI3K/AKT signaling pathway in septic mice with acute respiratory distress syndrome

“…Moreover, AKT is generally recognized as a key factor in PI3K (phosphatidylinositol 3-kinase) /AKT pathway and acts as a crucial role in cell differentiation, proliferation, metabolism, apoptosis, protein synthesis and transcription [11]. Previous studies have indicated that ARDS can be treated by the inhibition of PI3K/AKT signaling pathway [15][16][17][18].…”