Calcium-Independent Phospholipase A2β Is Dispensable in Inflammasome Activation and Its Inhibition by Bromoenol Lactone

摘要: Calcium-independent phospholipase A2 (iPLA2) has been suggested to play an important role in the activation of caspase-1 induced by lipopolysaccharides (LPS). Here, we used pharmacological and genetic approaches study iPLA2 caspase-1. Bromoenol lactone (BEL), inhibitor that was originally support a for secretion IL-1β, prevented LPS ATP as described, also triggered Salmonella infection cytosolic flagellin, which rely on Nlrc4 inflammasome. Analysis BEL enantiomers showed S-BEL form more effective than R-BEL inhibiting inflammasome, suggesting iPLA2β. However, IL-1β their inhibition were unimpaired macrophages deficient identified serine proteases. Consistent with latter, proteases inhibitors TPCK, TLCK AAF-cmk Nlrp3 inflammasomes while pan-cathepsin ineffective. These results indicate iPLA2β is not critical currently proposed. Instead, suggest protease(s) targeted may inflammasome microbial stimuli.