Lipopolysaccharide Induces Autophagic Cell Death through the PERK-Dependent Branch of the Unfolded Protein Response in Human Alveolar Epithelial A549 Cells.

摘要: Background: Alveolar epithelial cell death plays a critical role in the pathogenesis of lipopolysaccharide (LPS)-induced acute lung injury. Increased autophagy has dual effect on survival. However, it is not known whether promotes or survival human alveolar cells exposed to LPS. Methods: Genetic and pharmacological approaches were used evaluate A549 viability upon LPS exposure. The endoplasmic reticulum (ER) stress unfolded protein response (UPR) pathways examined with immunoblotting studies further explore underlying mechanisms. Results: Treatment (50 µg/ml) led activation decreased cells. Blocking via short interfering RNA inhibitor significantly decreased, whereas rapamycin increased, LPS-induced viability. ER was activated LPS-stimulated cells, reduced autophagy. only PERK pathway had rarely ATF6 IRE1 branches UPR Moreover, knockdown ATF4 attenuated promoted Conclusion: In induces autophagic that depends branch stress.