Activation of Alpha-7 Nicotinic Acetylcholine Receptors (α7nAchR) Promotes the Protective Autophagy in LPS-Induced Acute Lung Injury (ALI) In Vitro and In Vivo

Abstract The release of inflammatory cytokines and chemokines and autophagy has been reported to be involved in the pathogenic mechanism of acute lung injury (ALI). Reportedly, alpha-7 nicotinic acetylcholine receptors (alpha 7nAchR) might play a protective role in LPS-induced ALI. In the current research, we established LPS-induced ALI model in mice and alpha 7nAchR agonist PNU-282987 improved LPS-induced injury. In MH-S cells, LPS stimulation inhibited, whereas alpha 7nAchR agonist PNU-282987 enhanced the autophagy. alpha 7nAchR agonist PNU-282987 protected MH-S cells from LPS-induced inflammation by reducing the concentrations of IL-6, TNF-alpha, and IL-1 beta. Finally, LPS stimulation dramatically inhibited MH-S cell viability but enhanced cell apoptosis, whereas PNU-282987 treatment exerted opposite effects; alpha 7nAchR might regulate the cellular homeostasis via affecting the crosstalk between the autophagy and apoptosis in MH-S cells; in other words, alpha 7nAChR agonist enhances MH-S cell autophagy and inhibits MH-S cell apoptosis. In conclusion, alpha 7nAchR promote the protective autophagy in LPS-induced ALI model in mice and MH-S cells. The application of alpha 7nAchR agonist is considered a potent target for LPS-induced ALI, which needs further clinical investigation.