Figure 6.
Compounds 14 and 17 block NLRP3 inflammasome activation and IL-1β production in primary macrophages and LPS-challenged mice. (A) BMDMs were primed with LPS (1 μg/mL) for4.5 h and then treated with indicated doses of 14 or 17 when adding ATP (5 mM) stimulation for 30 min. IL-β in the culture media was assayed by ELISA. (B and C) J774A.1 cells were treated with LPS (1 μg/mL) and test compounds (10 μM) for 1 h. Flagellin (1 μg/mL) was added and allowed to incubate for 6 h or (poly(dA:dT)) (4 μg/mL) for 8 h. The supernatants were collected, and levels of IL-1β were measured by ELISA. (D) Serum levels of IL-1β from C57BL/6 mice pretreated with 14 and 17 (0.5 mg/kg) or vehicle control were measured by ELISA 2.5 h after i.p. injection of LPS (20 mg/kg).