NLRP3 inflammasome induces PCSK9 expression. (A) and (B) NLRP3 and PCSK9 expression in LPS primed macrophages treated with ATP or nigericin. (C) PCSK9 expression (intracellular, measured by western blot) and its secretion (extracellular, measured by ELISA) from LPS-primed MPMs treated with ATP or nigericin. (D) Pearson correlation coefficient (R) analysis for the correlation between intracellular expression and its release based on the results from panels C. (E) and (F) Release of IL-1β and IL-18 from LPS-primed MPMs treated with ATP or nigericin. Cytokine levels were normalized to that in DMSO-treated cells. (G) and (H) Effect of NLRP3 inflammasome specific inhibitor MCC950 on PCSK9 secretion from LPS-primed MPMs treated with ATP or nigericin. (I) Effect of PCSK9 gene deletion on expression of NLRP3 and IL-1β. Western blots in each group were performed with the same protein concentration and the same film exposure time. Data represent the mean ± SD of independent experiments (n=5 mice per genotype), each performed in triplicate. *P<0.05, **P<0.01, ***P<0.001, ****P<0.0001 vs. indicated group. MPMs: mouse peritoneal macrophages.