Article

Protective effects of specific cannabinoid receptor 2 agonist GW405833 on concanavalin A-induced acute liver injury in mice

Authors: Ze-bing Huang1,2, Yi-xiang Zheng1,2, Ning Li3, Sheng-lan Cai1,2, Yan Huang1,2, Juan Wang1,2, Xing-wang Hu1,2, Yang Wang2,4, Jie Wu1,5, Xue-gong Fan1,2
1 Department of Infectious Diseases, Xiangya Hospital, Central South University, Changsha 410008, China
2 Hunan Key Laboratory of Viral Hepatitis, Xiangya Hospital, Central South University, Changsha 410008, China
3 Department of Blood Transfusion, Xiangya Hospital, Central South University, Changsha 410008, China
4 Institude of Integrative Medicine, Xiangya Hospital, Central South University, Changsha 410008, China
5 Departments of Neurology and Neurobiology, Barrow Neurological Institute, St. Joseph’s Hospital and Medical Center, Phoenix, AZ 85013, USA
Correspondence to: Jie Wu: jiewubni@gmail.com, Xue-gong Fan: xgfan@hotmail.com,
DOI: 10.1038/s41401-019-0213-0
Received: 10 February 2018
Accepted: 16 January 2019
Advance online: 27 March 2019

Abstract

Cannabinoid receptor 2 (CB2R) is highly expressed in immune cells and plays an important role in regulating immune responses. In the current study, we investigated the effects of GW405833 (GW), a specific CB2R agonist, on acute liver injury induced by concanavalin A (Con A). In animal experiments, acute liver injury was induced in mice by injection of Con A (20 mg/kg, i.v.). The mice were treated with GW (20 mg/kg, i.p., 30 min after Con A injection) or GW plus the selective CB2R antagonist AM630 (2 mg/kg, i.p., 15 min after Con A injection). We found that Con A caused severe acute liver injury evidenced by significantly increased serum aminotransferase levels, massive hepatocyte apoptosis, and necrosis, as well as lymphocyte infiltration in liver tissues. Treatment with GW significantly ameliorated Con A-induced pathological injury in liver tissue, decreased serum aminotransferase levels, and decreased hepatocyte apoptosis. The therapeutic effects of GW were prevented by AM630. In cell experiments, we showed that CB2Rs were highly expressed in Jurkat T cells, but little expression in L02 liver cells. Treatment with GW (10−40 μg/mL) dose-dependently decreased the viability of Jurkat T cells and induced cell apoptosis, which was reversed by AM630. In the coculture of Jurkat T cells with L02 liver cells, GW dose-dependently protected L02 cells from apoptosis induced by Con A (5 μg/mL). The protective effect of GW was reversed by AM630 (1 μg/mL). Our results suggest that GW protects against Con A-induced acute liver injury in mice by inhibiting Jurkat T-cell proliferation through the CB2Rs.
Keywords: cannabinoid receptor 2; GW405833; AM630; Concanavalin A; acute liver injury; Jurkat T cells; L02 liver cells

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