Cannabinoid receptor 2 promotes the intracellular degradation of HMGB1 via the autophagy-lysosome pathway in macrophage

•CB2R agonist treatment decreased LPS-induced HMGB1 secretion but not influencing HMGB1 mRNA in peritoneal macrophages.•The autophagy-lysosome pathway but not ubiquitination pathway was involved in CB2R-mediated HMGB1 degradation.•Activation of CB2R promoted the integrity of autophagy flux in macrophages.•Inhibition of autophagy blocked GW-induced nuclear translocation of HMGB1 in macrophages.•CTSB was involved in the degradation of HMGB1.