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RESEARCH PRODUCT
Potassium regulates IL-1 beta processing via calcium-independent phospholipase A2.
Susanne StrauchIwan WalevSucharit BhakdiAngela ValevaJochen KleinMatthias HusmannOksana WeichelHeiner Wirtzsubject
Intracellular FluidPotassiumImmunologychemistry.chemical_elementNaphthalenesCleavage (embryo)MonocytesPhospholipases APhospholipase A2Calcium-Independent Phospholipase A2Immunology and AllergyHumansCells Culturedchemistry.chemical_classificationCalcium metabolismbiologyTumor Necrosis Factor-alphaCaspase 1Biological TransportCaspase InhibitorsCell biologyEnzyme ActivationPhospholipases A2EnzymechemistryPyronesbiology.proteinPotassiumCalciumEffluxBromoenol lactoneProtein Processing Post-TranslationalImmunosuppressive AgentsInterleukin-1description
Abstract 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-1β 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-1β and formation of glycerophosphocholine were blocked by bromoenol lactone, the specific iPLA2 inhibitor. Bromoenol lactone-dependent inhibition of IL-1β processing was not due to perturbation of the export machinery for pro-IL-1β and IL-1β or to caspase-1 suppression. Conspicuously, activation of Ca2+-dependent phospholipase A2 did not support but rather suppressed IL-1β processing. Thus, our findings reveal a specific role for iPLA2 activation in the sequence of events underlying IL-1β maturation.
| year | journal | country | edition | language |
|---|---|---|---|---|
| 2000-05-09 | Journal of immunology (Baltimore, Md. : 1950) |