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

Shao,Zhenzhen; Li,Quan; Wang,Shuang; Chen,Zhixia

doi:10.3892/mmr.2019.10016

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

Authors:
- Zhenzhen Shao
- Quan Li
- Shuang Wang
- Zhixia Chen
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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
Published online on: March 12, 2019 https://doi.org/10.3892/mmr.2019.10016
Pages: 3791-3798
Copyright: © Shao et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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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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