Effects of autophagy on LPS-induced lung inflammation and acute lung injury (ALI) in vitro and in vivo

Background: ALI refers to acute and progressive hypoxic respiratory failure due to various pathogenic factors outside the cardiomyopathy which associated the increased oxidative stress and inflammation in the lung tissue, but the mechanism is still unclear. Aim: This study explored the role of autophagy in LPS-induced lung injury. Our previous studies showed that autophagy was associated with the inflammation and oxidative stress. In the current study, we investigated the effects of autophagy on LPS-induced inflammation of A549 cells and lung injury of mice. Results: LPS significantly increased autophagy activation in vitro and vivo. After using the agonist to promote autophagy, LPS-induced A549 cell inflammatory response and LPS-induced lung injury in mice were significantly reduced, pro-inflammatory cytokines TNF-α and IL-6 also decreased significantly, while the autophagy inhibitor had the opposite effects. Promoting autophagy also suppressed the elevation of oxidative stress induced by LPS. Further study found that increasing autophagy could effectively inhibit ERK, p38 mitogen-activated protein kinase (MAPK) pathway and TLR4/MYD88 pathway, thereby inhibited the downstream NF-κB pathway. While, the inhibition of autophagy had the opposite effects. Finally, we found that the inhibition of the MAPK or TLR4/MYD88 pathways by inhibitors suppressed the level of the NF-κB pathway which closely associated with inflammation and significantly reduced the activation of autophagy induced by LPS. Conclusion: The results has demonstrated that autophagy is activated and has protective effects in LPS-induced ALI, activation of autophagy may be helpful for the treatment.