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Inflammation

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

  • Xin Zhao
  • Zhizhong Yu
  • Zheng Lv
  • Lei Meng
  • Jiaxin Xu
  • Shiying Yuan
  • Zhaohui FuEmail author
Original Article
  • 41 Downloads

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 (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.

KEY WORDS

acute lung injury (ALI) autophagy alpha-7 nicotinic acetylcholine receptors (α7nAchR) apoptosis 

Notes

Compliance with Ethical Standards

Conflict of Interest

The authors declare that they have no conflict of interest.

Ethical Approval

All applicable international, national, and/or institutional guidelines for the care and use of animals were followed.

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Copyright information

© Springer Science+Business Media, LLC, part of Springer Nature 2019

Authors and Affiliations

  • Xin Zhao
    • 1
    • 2
  • Zhizhong Yu
    • 1
    • 2
  • Zheng Lv
    • 1
    • 2
  • Lei Meng
    • 1
    • 2
  • Jiaxin Xu
    • 1
    • 2
  • Shiying Yuan
    • 1
    • 2
  • Zhaohui Fu
    • 1
    • 2
    Email author
  1. 1.Department of Critical Care Medicine, Union Hospital, Tongji Medical CollegeHuazhong University of Science and TechnologyWuhanPeople’s Republic of China
  2. 2.Institute of Anesthesia and Critical Care Medicine, Union Hospital, Tongji Medical CollegeHuazhong University of Science and TechnologyWuhanChina

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