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

Ze bing Huang, Yi xiang Zheng, Ning Li, Sheng lan Cai, Yan Huang, Juan Wang, Xing wang Hu, Yang Wang, Jie Wu, Xue gong Fan

Research output: Contribution to journalArticlepeer-review

11 Scopus citations

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.

Original languageEnglish (US)
Pages (from-to)1404-1411
Number of pages8
JournalActa Pharmacologica Sinica
Volume40
Issue number11
DOIs
StatePublished - Nov 1 2019
Externally publishedYes

Keywords

  • acute liver injury
  • AM630
  • cannabinoid receptor 2
  • Concanavalin A
  • GW405833
  • Jurkat T cells
  • L02 liver cells

ASJC Scopus subject areas

  • Pharmacology
  • Pharmacology (medical)

Fingerprint

Dive into the research topics of 'Protective effects of specific cannabinoid receptor 2 agonist GW405833 on concanavalin A-induced acute liver injury in mice'. Together they form a unique fingerprint.

Cite this