Potassium regulates IL-1 beta processing via calcium-independent phospholipase A(2)

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 r ole 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 level s of glycerophosphocholine, an unambiguous indicator of phospholipase A(2) activation. Both maturation of IL-1 beta and formation of glycerophosphocho line were blocked by bromoenol lactone, the specific iPLA(2) inhibitor. Bro moenol 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 phosphol ipase 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 sequen ce of events underlying IL-1 beta maturation.