Potassium regulates IL-1β processing via calcium-independent phospholipase A2

We report that potassium leakage from cells leads to activation of the Ca2+-independent phospholipase A(2) (iPLA(2)), and the latter plays a pivotal role in regulating the cleavage of pro-IL-1 beta by the IL-converting enzyme caspase-1 in human monocytes, K+ efflux led to increases of cellular levels of glycerophosphocholine, an unambiguous indicator of phospholipase A(2) activation. Both maturation of IL-1 beta and formation of glycerophosphocholine were blocked by bromoenol lactone, the specific iPLA(2) inhibitor. Bromoenol lactone-dependent inhibition of IL-1 beta processing was not due to perturbation of the export machinery for pro-IL-1 beta and IL-1 beta or to caspase-1 suppression. Conspicuously, activation of Ca2+-dependent phospholipase A(2) did not support but rather suppressed IL-1 beta processing. Thus, our findings reveal a specific role for iPLA(2), activation in the sequence of events underlying IL-1 beta maturation.