Fig. 5
AMPK activates p38 MAPK through the inhibition of HMGCR to regulate the expression of PD-1. A Western blot analysis of the expression of PD-1 in treatment with the AMPK modulators: AICAR and compound C and the mevalonate pathway byproducts: cholesterol, GGPP, and mevalonate. B Immunoblot analysis of phosphorylated and total ERK, JNK, and p38 MAPK in Tregs from WT and AMPKfl/flFoxp3-Cre mice after 1 h of resting and 3 h of stimulation with anti-CD3/CD28. Western blot analysis of phosphorylated and total p38 MAPK in WT Tregs treated with or without C AICAR or D compound C at the indicated doses. E Immunoblot analysis of phosphorylated and total ERK and JNK in WT Tregs treated with AICAR, compound C, or statin. F Immunoblot analysis of phosphorylated and total form of p38 in Tregs treated with different concentrations of statin. G Immunoblot analysis of PD-1 in Tregs treated with SB203580 at the indicated doses. H MFI of PD-1 in WT Tregs with or without SB203580 treatment. The I tumor volume and J weight of B16F10 melanoma tumors in WT mice treated with PBS or SB203580. K MFI of PD-1 in Tregs isolated from tumor tissues after treatment with PBS or SB203580. The data are presented as the mean ± standard deviation (SD); n = 5 mice per group. *P < 0.05; **P < 0.01; ***P < 0.001