Potassium regulates IL-1 beta processing via calcium-independent phospholipase A2.
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-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 A2 activation. Both maturation of IL-1 beta and formation of glycerophosphocholine were blocked by bromoenol lactone, the specific iPLA2 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 A2 did not support but rather suppressed IL-1 beta processing. Thus, our findings reveal a specific role for iPLA2 activation in the sequence of events underlying IL-1 beta maturation.
Walev
I
I
Institute of Medical Microbiology, Hygiene and Pharmacological Institute, Johannes Gutenberg University, Mainz, Germany.
Klein
J
J
Husmann
M
M
Valeva
A
A
Strauch
S
S
Wirtz
H
H
Weichel
O
O
Bhakdi
S
S
D001692:Biological Transport / Q000187:drug effects / Q000276:immunology; D002118:Calcium / Q000378:metabolism / Q000502:physiology*; D020170:Caspase 1 / Q000378:metabolism; D061945:Caspase Inhibitors; D002478:Cells, Cultured; D004789:Enzyme Activation / Q000187:drug effects / Q000276:immunology; D006801:Humans; D007166:Immunosuppressive Agents / Q000494:pharmacology; D007375:Interleukin-1 / Q000037:antagonists & inhibitors / Q000378:metabolism*; D007424:Intracellular Fluid / Q000201:enzymology / Q000276:immunology / Q000378:metabolism; D009000:Monocytes / Q000187:drug effects / Q000201:enzymology / Q000276:immunology / Q000378:metabolism; D009281:Naphthalenes / Q000494:pharmacology; D010741:Phospholipases A / Q000037:antagonists & inhibitors / Q000502:physiology*; D054467:Phospholipases A2; D011188:Potassium / Q000378:metabolism / Q000502:physiology*; D011499:Protein Processing, Post-Translational / Q000276:immunology*; D011753:Pyrones / Q000494:pharmacology; D014409:Tumor Necrosis Factor-alpha / Q000037:antagonists & inhibitors / Q000378:metabolism
D061945:Caspase Inhibitors; D007166:Immunosuppressive Agents; D007375:Interleukin-1; D009281:Naphthalenes; D011753:Pyrones; D014409:Tumor Necrosis Factor-alpha; C068314:6-(bromomethylene)tetrahydro-3-(1-naphthaleneyl)-2H-pyran-2-one; D010741:Phospholipases A; D054467:Phospholipases A2; D020170:Caspase 1; D011188:Potassium; D002118:Calcium