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Human monocyte stimulus-coupled IL-1beta posttranslational processing: modulation via monovalent cations.

D G Perregaux·C A Gabel
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Abstract

Lipopolysaccharide-activated human monocytes produce prointerleukin (pro-IL)-1beta but release little of this inflammatory cytokine as the biologically active species. Efficient externalization of mature 17-kDa cytokine requires that the activated monocytes encounter a secondary stimulus such as ATP. To identify cation requirements of the ATP-induced process, lipopolysaccharide-activated monocytes were treated with ATP in media containing different Cl- salts or sucrose. Media devoid of Na+ did not support IL-1beta processing. Titration of NaCl into choline chloride- or sucrose-based media restored 17-kDa IL-1beta production. Na+ replacement, however, was not sufficient to support ATP-induced production of 17-kDa IL-1beta in the presence of >/=37 mM extracellular K+ or Li+. Inhibition by K+ suggests that efflux of this cation is a necessary component of the stimulus-coupled response. The inhibitory effect achieved by Na+ depletion is not due to inactivation of the ATP receptor and is distinct from a caspase-1 inhibitor. Stimulus-coupled IL-1beta posttranslational processing, therefore, requires extracellular Na+ for a step downstream of the initiating stimulus but preceding caspase-1 activation.

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Adenosine TriphosphateCations, MonovalentCellular SenescenceCulture MediaHumansInterleukin-1MonocytesProtein PrecursorsProtein Processing, Post-TranslationalReceptors, Purinergic P2Receptors, Purinergic P2X7SodiumJournal Article

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D G Perregaux, C A Gabel. 1998. Human monocyte stimulus-coupled IL-1beta posttranslational processing: modulation via monovalent cations.. https://doi.org/10.1152/ajpcell.1998.275.6.c1538

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