The antidiabetic drug metformin inhibits IL-1β and IL-18 production induced by various inflammasome stimuli in LPS-primed
MDMs. Primary MDMs from healthy controls (n = 5) were primed with LPS (10 ng/mL for 4 h) in the presence of a high glucose concentration (15 mmol/L). They were then
treated with metformin (Met) at the indicated doses (A, B, and D; 200 and 500 μmol/L for 60 min) or for the indicated periods of time (C; 200 μmol/L for 30, 60, or 120 min), and stimulated with ATP (A–C; 1 mmol/L for 1 h), MSU (C and D; 100 μg/mL for 6 h), or FFAs (D; 200 μmol/L for 16 h). A: Quantitative real-time RT-PCR analysis of Il1β and IL8 mRNA levels. B and D: ELISA analysis of IL-1β and IL-18. C: Western blotting analysis of IL-1β protein levels in cell lysates (Cell, pro-IL-1β [31 kDa]) and supernatants (SN; mature
IL-1β [17 kDa]). A, B, and D: Data are expressed as means ± SEM of five independent experiments. ***P < 0.001 vs. solvent control (SC). U, untreated.