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

Abstract
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.
AuthorsA P Liu, Q H Yuan, B Zhang, L Yang, Q W He, K Chen, Q S Liu, Z Li, J Zhan
JournalCellular signalling (Cell Signal) Vol. 69 Pg. 109556 (05 2020) ISSN: 1873-3913 [Electronic] England
PMID32027949 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
CopyrightCopyright © 2020. Published by Elsevier Inc.
Chemical References
  • Cannabinoid Receptor Agonists
  • Cannabinoids
  • Cnr2 protein, mouse
  • Cytokines
  • Inflammation Mediators
  • Receptor, Cannabinoid, CB2
  • HU 308
Topics
  • Acute Lung Injury (drug therapy)
  • Animals
  • Autophagy (drug effects)
  • Cannabinoid Receptor Agonists (pharmacology)
  • Cannabinoids (pharmacology)
  • Cytokines (immunology)
  • Immunosuppression Therapy (methods)
  • Inflammation Mediators (immunology)
  • Male
  • Mice
  • Mice, Inbred C57BL
  • RAW 264.7 Cells
  • Receptor, Cannabinoid, CB2 (agonists)
  • Sepsis (drug therapy)

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