Figure 1.
MCC950 impedes NLRP3 inflammasome activation in response to LPS + Aβ. BMDMs, isolated from the femurs and tibias of mice, were cultured for 7 days as described in the Methods (section 2.2). BMDMs were primed with LPS (100 ng/ml) for 3 h, pre-treated with MCC950 (100 nM) for 30 min and subsequently incubated with Aβ (10 µM) for 24 h. Cell supernatants were collected for analysis by ELISA or harvested for RT-PCR analysis. LPS + Aβ increased IL-1β (a), IL-1β mRNA (b), TNFα (c), TNFα mRNA (d), IL-6 (e), IL-6 mRNA (f), IL-10 (g) and IL-10 mRNA (h) (**p < 0.01, ***p < 0.001; Con vs LPS + Aβ). MCC950 decreased the LPS + Aβ-induced IL-1β secretion (a; ###p < 0.001; LPS + Aβ vs LPS + Aβ + MCC950). MCC950 has no effect on any other LPS + Aβ-induced changes. Data are expressed as the mean ± S.E.M. and analysed using a two-way ANOVA and Bonferroni post hoc test; n = 6–7 mice/group.