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Cannabinoid receptor 2 activation alleviates septic lung injury by promoting autophagy via inhibition of inflammatory mediator release
Affiliation:1. Department of Medicine, Baylor College of Medicine, University of Houston Medical School, Houston, TX, USA;2. Pathology & Laboratory Medicine Department, University of Houston Medical School, Houston, TX, USA;1. Department of Pharmacology and Toxicology, Faculty of Pharmacy, Zagazig University, Zagazig 44519, Egypt;2. Department of Biochemistry, Faculty of Pharmacy, Zagazig University, Zagazig, Egypt;3. Department of Histology, Faculty of Medicine for Girls, Al-Azhar University, Cairo, Egypt;1. Department of Pharmacology, Ataturk University Faculty of Medicine, 25240 Erzurum, Turkey;2. Department of Pharmacology, Kafkas University Faculty of Medicine, 36240 Kars, Turkey;3. Department of Histology and Embryology, Ataturk University Faculty of Medicine, 25240 Erzurum, Turkey;4. Department of Biochemistry, Ataturk University Faculty of Pharmacy, 25240 Erzurum, Turkey;5. Department of Pharmacology and Toxicology, Ataturk University Faculty of Veterinary Medicine, 25240 Erzurum, Turkey;6. Department of Pharmacology, RTE University Faculty of Medicine, 53240 Rize, Turkey;7. Department of Histology and Embryology, 19 Mart University, Faculty of Medicine, 25240 Çanakkale, Turkey;1. Department of Anesthesiology and Pain Medicine, School of Medicine, Chosun University, Gwangju 501-759, Republic of Korea;2. College of Pharmacy, Research Institute of Pharmaceutical Sciences, Seoul National University, Seoul 151-742, Republic of Korea;3. School of Medicine, Chosun University, Gwangju 501-759, Republic of Korea
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.
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