Cannabinoid receptor 2 activation alleviates septic lung injury by promoting autophagy via inhibition of inflammatory mediator release

Septic lung injury is one of main causes of high mortality in severe patients. Inhibition of excessive inflammatory response is considered as an effective strategy for septic lung injury. Previous studies have shown that cannabinoid receptor 2 (CB2), a G protein-coupled receptor, play an important r...

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Bibliographic Details
Published in:Cellular signalling 2020-05, Vol.69, p.109556-109556, Article 109556
Main Authors: Liu, A.P., Yuan, Q.H., Zhang, B., Yang, L., He, Q.W., Chen, K., Liu, Q.S., Li, Z., Zhan, J.
Format: Article
Language:English
Subjects:
Acute lung injury
Autophagy
Cannabinoid receptor 2
Inflammation
Sepsis
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Summary:Septic lung injury is one of main causes of high mortality in severe patients. Inhibition of excessive inflammatory response is considered as an effective strategy for septic lung injury. Previous studies have shown that cannabinoid receptor 2 (CB2), a G protein-coupled receptor, play an important role in immunosuppression. Whether CB2 can be used as a therapeutic target for septic lung injury is unclear. The aim of this study is to explore the role of CB2 in sepsis and its potential mechanism. In this study, treatment with HU308, a specific agonist of CB2, could reduce lung pathological injury, decrease the level of inflammatory cytokines and strengthen the expression of autophagy-related gene after cecal ligation puncture (CLP)-induced sepsis in mice. Similar results were obtained in RAW264.7 macrophages after LPS treatment. Furthermore, the effect of HU308 could be blocked by autophagy blocker 3-MA in vivo and in vitro. These results suggest that CB2 serves as a protective target for septic lung injury by decreasing inflammatory factors, which is associated with the enhancement of autophagy. [Display omitted] •Activation of cannabinoid receptor 2 can alleviate sepsis-induced lung injury.•Cannabinoid receptor 2 may alleviate sepsis-induced lung injury via inhibition of inflammatory mediator release.•Cannabinoid receptor 2 inhibits the release of inflammatory cytokines by promoting autophagy in vivo and vitro.
ISSN:0898-6568
1873-3913
DOI:10.1016/j.cellsig.2020.109556