AMPK-mTOR-P70S6K signaling cascades are involved in the regulation of CB2R on autophagy both in intro and in vivo.

Peritoneal macrophages from WT and CB2R KO mice were isolated and primed with LPS (10 ng/ml) for 1 h, and then were stimulated with 3% DSS. Colon tissues were isolated from mice at day 8 after DSS-induced colitis. The expression of p-AMPK/AMPK, p-mTOR/mTOR and p-P70S6K/P70S6K in macrophages and colon tissues were analyzed using Western blot. (A) In colon from DSS-induced colitis mice, the level of p-AMPK was decreased and the levels of p-mTOR and p-P70S6K were increased in CB2R KO mice when compared with those from WT mice. n = 6 per group. *P<0.05 vs. control. (B) Compared to WT macrophages, the level of p-AMPK was decreased and the level of p-mTOR and p-P70S6K were increased in CB2R KO group after LPS/DSS stimulation. n = 6 per group. **P<0.01 vs. control; #P<0.05 vs. WT, ##P<0.01 vs. WT. (C) In peritoneal macrophages isolated from C57BL/6 mice, HU 308 decreased the levels of NLRP3, Casp-1 p20/Casp-1 p45 ratio and proIL-1β induced by LPS/DSS. Compound C, an inhibitor of AMPK, partly blocked the inhibitory effects of HU 308 on NLRP3, Casp-1 p20/Casp-1 p45 ratio and proIL-1β.