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Potassium Regulates IL-1ß Processing Via Calcium-Independent Phospholipase A₂¹

Iwan Walev^2,*, Jochen Klein, Matthias Husmann^*, Angela Valeva^*, Susanne Strauch^*, Heiner Wirtz^*, Oksana Weichel^* and Sucharit Bhakdi^*

^* Institute of Medical Microbiology and Hygiene and Pharmacological Institute, Johannes Gutenberg University, Mainz, Germany

We report that potassium leakage from cells leads to activation of the Ca²⁺-independent phospholipase A₂ (iPLA₂), and the latter plays a pivotal role in regulating the cleavage of pro-IL-1ß 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 A₂ activation. Both maturation of IL-1ß and formation of glycerophosphocholine were blocked by bromoenol lactone, the specific iPLA₂ inhibitor. Bromoenol lactone-dependent inhibition of IL-1ß processing was not due to perturbation of the export machinery for pro-IL-1ß and IL-1ß or to caspase-1 suppression. Conspicuously, activation of Ca²⁺-dependent phospholipase A₂ did not support but rather suppressed IL-1ß processing. Thus, our findings reveal a specific role for iPLA₂ activation in the sequence of events underlying IL-1ß maturation.

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