Autophagy inhibition protects from alveolar barrier dysfunction in LPS-induced ALI mice by targeting alveolar epithelial cells.

Objective: The aim of this study was to investigate whether autophagy is enhanced in alveolar epithelial cells as well as its role in alveolar barrier function of in lipopolysaccharide (LPS)-induced ALI mice. Materials and methods: Autophagy inhibitors, including 3-methyladenine (3-MA) and chloroquine (CLQ), and LPS were intraperitoneally administered to mice. Histological evaluation and confocal microscopy, Western blot, transmission electron microscopy, and ELISA were performed for analysis. First, the mouse model of ALI was established. Then, autophagy level changes in the mouse lung as well as the effects of autophagy inhibition on indirect ALI and alveolar epithelial barrier function induced by LPS were assessed. Finally, pro-inflammatory factors in BALF from ALI mice after autophagy inhibition by 3-MA or CLQ administration were detected. Results: The experimental animal model of LPS-induced ALI had the expected features. In addition, autophagy in alveolar epithelial cells in ALI mice was enhanced. Furthermore, autophagy in alveolar epithelial cells promoted alveolar epithelial barrier dysfunction in LPS-induced ALI. Finally, autophagy inhibition resulted in reduced LPS-induced lung tissue inflammation. Conclusion: These findings suggest that autophagy inhibition protects from alveolar barrier dysfunction in LPS-induced ALI mice by targeting alveolar epithelial cells.