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Article

Protective effects of PNU‑282987 on sepsis‑induced acute lung injury in mice

  • Authors:
    • Zhenzhen Shao
    • Quan Li
    • Shuang Wang
    • Zhixia Chen
  • View Affiliations / Copyright

    Affiliations: Department of Anesthesiology, National Cancer Center/Cancer Hospital and Shenzhen Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Shenzhen, Guangdong 518116, P.R. China
    Copyright: © Shao et al. This is an open access article distributed under the terms of Creative Commons Attribution License.
  • Pages: 3791-3798
    |
    Published online on: March 12, 2019
       https://doi.org/10.3892/mmr.2019.10016
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Abstract

The cholinergic anti‑inflammatory pathway is considered an attractive approach for the alleviation of inflammatory diseases. Sepsis is characterized by systemic inflammation and widespread organ injury, especially that in the lung. In the present study, we explored the effects of an α7nAChR agonist, PNU‑282987, on sepsis‑induced lung injury and investigated the mechanisms of PNU‑282987 in response to lipopolysaccharide (LPS) stimulation in peritoneal macrophages. Sepsis was induced in C57BL/6 mice via cecal ligation puncture (CLP). Fifty mice were randomly divided into five groups: The sham group treated with vehicle, the sham group treated with PNU‑282987, the CLP group treated with vehicle, and the CLP group treated with PNU‑282987 (1 mg/kg) 1 h before or 2 h after surgery. All mice were sacrificed at 12 or 24 h after CLP. Both pre‑ and post‑CLP treatment with PNU‑282987 significantly attenuated sepsis‑induced lung injury and the release of IL‑6 in the bronchoalveolar lavage fluid (BALF). Pre‑treatment with PNU‑282987 also inhibited sepsis‑increased TNF‑α and IL‑6 production, while post‑CLP treatment only inhibited IL‑6 production in the lung tissue. Neither pre‑ nor post‑CLP treatment with PNU‑282987 affected IL‑6 release in the serum. Furthermore, pretreatment with PNU‑282987 resulted in reductions in TNF‑α and IL‑6 release in a dose‑ and time‑dependent manner and decreased the phosphorylation levels of p38, JNK and ERK under LPS conditions in peritoneal macrophages. Our results demonstrate that activation of α7nAChR alleviates sepsis‑induced lung injury; this effect is associated with the suppression of inflammatory responses via the MAPK pathway, suggesting that α7nAChR is a potential therapeutic target for the treatment of sepsis.
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Copy and paste a formatted citation
Spandidos Publications style
Shao Z, Li Q, Wang S and Chen Z: Protective effects of PNU‑282987 on sepsis‑induced acute lung injury in mice. Mol Med Rep 19: 3791-3798, 2019.
APA
Shao, Z., Li, Q., Wang, S., & Chen, Z. (2019). Protective effects of PNU‑282987 on sepsis‑induced acute lung injury in mice. Molecular Medicine Reports, 19, 3791-3798. https://doi.org/10.3892/mmr.2019.10016
MLA
Shao, Z., Li, Q., Wang, S., Chen, Z."Protective effects of PNU‑282987 on sepsis‑induced acute lung injury in mice". Molecular Medicine Reports 19.5 (2019): 3791-3798.
Chicago
Shao, Z., Li, Q., Wang, S., Chen, Z."Protective effects of PNU‑282987 on sepsis‑induced acute lung injury in mice". Molecular Medicine Reports 19, no. 5 (2019): 3791-3798. https://doi.org/10.3892/mmr.2019.10016
Copy and paste a formatted citation
x
Spandidos Publications style
Shao Z, Li Q, Wang S and Chen Z: Protective effects of PNU‑282987 on sepsis‑induced acute lung injury in mice. Mol Med Rep 19: 3791-3798, 2019.
APA
Shao, Z., Li, Q., Wang, S., & Chen, Z. (2019). Protective effects of PNU‑282987 on sepsis‑induced acute lung injury in mice. Molecular Medicine Reports, 19, 3791-3798. https://doi.org/10.3892/mmr.2019.10016
MLA
Shao, Z., Li, Q., Wang, S., Chen, Z."Protective effects of PNU‑282987 on sepsis‑induced acute lung injury in mice". Molecular Medicine Reports 19.5 (2019): 3791-3798.
Chicago
Shao, Z., Li, Q., Wang, S., Chen, Z."Protective effects of PNU‑282987 on sepsis‑induced acute lung injury in mice". Molecular Medicine Reports 19, no. 5 (2019): 3791-3798. https://doi.org/10.3892/mmr.2019.10016
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