Autophagy Decreases Alveolar Epithelial Cell Injury by Suppressing the NF-κB Signaling Pathway and Regulating the Release of Inflammatory Mediators

Abstract

To research the impact of autophagy on alveolar epithelial cell inflammation and its possible mechanism in early stages of hypoxia, we established a cell hypoxia-reoxygenation model and orthotopic left lung ischemia-reperfusion model. Rat alveolar epithelial cells stably expressing GFP-LC3 were treated with an autophagy inhibitor (3-methyladenine, 3-MA) or autophagy promoter (rapamycin), followed by hypoxia-reoxygenation treatment at 2, 4 and 6h in vitro. In vivo, twenty-four male Sprague-Dawley rats were randomly divided into four groups (model group: no blocking of hilum in the left lung; control group: blocking of hilum in the left lung for 1h with DMSO lavage; 3-MA group: blocking of hilum in the left lung for 1h with 100ml/kg of 3-MA (5mol/L) solution lavage; rapamycin group: blocking of hilum in the left lung for 1h with 100ml/kg of rapamycin (250nmol/L) solution lavage) to establish an orthotopic left lung ischemia model. This study demonstrated that rapamycin significantly suppressed the NF-{kappa}B signaling pathway, restrained the expression of pro-inflammatory factors. A contrary result was confirmed by 3-MA pretreatment. These findings indicate that autophagy reduces ischemia-reperfusion injury by repressing inflammatory signaling pathways in the early stage of hypoxia in vitro and in vivo. This could be a new protective method for lung ischemia-reperfusion injury.