Extended Data Fig. 2: Dimethyl malonate (DMM) decreases NLRP3 inflammasome activation.
From: Mitochondrial electron transport chain is necessary for NLRP3 inflammasome activation
a) Il1b mRNA expression (ΔΔCt) in BMDMs treated with LPS (100 ng/mL) for 4 hours, with or without DMM (10 mM) (N = 5 UT, LPS; N = 6 LPS + DMM). b) Tnf mRNA expression (ΔΔCt) in BMDMs treated as in a (N = 5 for all treatments). c) Il10 mRNA expression (ΔΔCt) in BMDMs treated as in a (N = 5 for all treatments). d) Pro-IL-1β protein levels in cell lysates of BMDMs treated with LPS (100 ng/mL), with or without DMM (10 mM). (N = 4 for all treatments). e) IL-1β protein levels in cell culture supernatant from BMDMs treated with LPS (100 ng/mL) and ATP (5 mM), with or without DMM (10 mM). (N = 5 for all treatments). f) TNFα protein levels in cell culture supernatant from BMDMs treated as in e. (N = 3 for all treatments). g) Intracellular pro-caspase-1 protein expression in cell lysates from BMDMs treated with or without LPS (100 ng/mL) and ATP (5 mM), with or without DMM (10 mM). (N = 3 for all treatments). h) Intracellular caspase-1 (p20 fragment) protein expression in cell lysates from BMDMs treated with or without LPS (100 ng/mL) and ATP (5 mM), with or without DMM (10 mM) (N = 3 for all treatments). Data are means + /− SEM. * p < 0.05, two-tailed t-test (e *p = 0.0001), one-way analysis of variance (ANOVA) with a Tukey test for multiple comparisons (h *p < 0.0001).
