Fig. 11.

Diagrammatic representation of the stimulatory effect of SP and IL-33 on IL-1β synthesis and secretion and the proposed point of inhibition of methoxyluteolin. Our evidence indicates that (1) SP and IL-33 activate their respective receptors and stimulate synthesis of procaspase-1 and pro-IL-1β, possibly via NF-κB, activation, which is inhibited by methoxyluteolin. (2) Procaspase-1 and pro-IL-1β are released from the nucleus, a process that could also be inhibited by methoxyluteolin. (3) In the cytoplasm, caspase-1, which is already active, converts pro-IL-1β to active IL-1β. (4) Some of the procaspase-1 is converted to caspase-1, but this may be a minor contribution since the NLRP3 inflammasome does not seem to be involved. (5) IL-1β and active caspase-1 are then secreted extracellularly, a process that is also inhibited by methoxyluteolin. Orange boxes and ovals indicate facts supported by our findings. Open boxes and ovals indicate pathways not supported by our data. The (T) attached to methoxyluteolin indicates possible points of inhibition.