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 (α7nAchR) might play a protective role in LPS-induced ALI. In the current research, we established LPS-induced ALI model in mice and α7nAchR agonist PNU-282987 improved LPS-induced injury. In MH-S cells, LPS stimulation inhibited, whereas α7nAchR agonist PNU-282987 enhanced the autophagy. α7nAchR agonist PNU-282987 protected MH-S cells from LPS-induced inflammation by reducing the concentrations of IL-6, TNF-α, and IL-1β. Finally, LPS stimulation dramatically inhibited MH-S cell viability but enhanced cell apoptosis, whereas PNU-282987 treatment exerted opposite effects; α7nAchR might regulate the cellular homeostasis via affecting the crosstalk between the autophagy and apoptosis in MH-S cells; in other words, α7nAChR agonist enhances MH-S cell autophagy and inhibits MH-S cell apoptosis. In conclusion, α7nAchR promote the protective autophagy in LPS-induced ALI model in mice and MH-S cells. The application of α7nAchR agonist is considered a potent target for LPS-induced ALI, which needs further clinical investigation.
Keywords: acute lung injury (ALI); alpha-7 nicotinic acetylcholine receptors (α7nAchR); apoptosis; autophagy.