Potassium-inhibited processing of IL-1 beta in human monocytes

EMBO J. 1995 Apr 18;14(8):1607-14.

Abstract

Agents that deplete cells of K+ without grossly disrupting the plasma membrane were found to stimulate the cleavage of pro-interleukin (IL)-1 beta to mature IL-1 beta. Agents examined in this study included staphylococcal alpha-toxin and gramicidin, both of which selectively permeabilize plasma membranes for monovalent ions, the ionophores nigericin and valinomycin, and the Na+/K+ ATPase inhibitor ouabain. K+ depletion by brief hypotonic shock also triggered processing of pro-IL-1 beta. The central role of K+ depletion for inducing IL-1 beta maturation was demonstrated in cells permeabilized with alpha-toxin: processing of pro-IL-1 beta was totally blocked when cells were suspended in medium that contained high K+, but could be induced by replacing extracellular K+ with Na+, choline+ or sucrose. To test whether K+ flux might also be important in physiological situations, monocytes were stimulated with lipopolysaccharide (LPS) for 1-2 h to trigger pro-IL-1 beta synthesis, and transferred to K(+)-rich medium. This maneuver totally suppressed IL-1 beta maturation. Even after 16 h, however, removal of K+ from the medium resulted in rapid processing and export of IL-1 beta. Ongoing export of mature IL-1 beta from cells stimulated with LPS for 2-6 h could also be arrested by transfer to K(+)-rich medium. Moreover, a combination of two K+ channel blockers inhibited processing of IL-1 beta in LPS-stimulated monocytes. We hypothesize that K+ movement and local K+ concentrations directly or indirectly influence the action of interleukin-1 beta-converting enzyme (ICE) and, possibly, of related intracellular proteases.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Antibody Specificity
  • Cell Membrane Permeability
  • Dose-Response Relationship, Drug
  • Enzyme-Linked Immunosorbent Assay
  • Humans
  • Interleukin-1 / biosynthesis*
  • Interleukin-1 / immunology
  • Interleukin-1 / metabolism*
  • Lipopolysaccharides / pharmacology
  • Monocytes / drug effects
  • Monocytes / physiology*
  • Potassium / metabolism
  • Potassium / pharmacology*
  • Potassium Channel Blockers
  • Protein Precursors / immunology
  • Protein Precursors / metabolism*
  • Protein Processing, Post-Translational / drug effects*
  • Type C Phospholipases

Substances

  • Interleukin-1
  • Lipopolysaccharides
  • Potassium Channel Blockers
  • Protein Precursors
  • interleukin 1 precursor
  • Type C Phospholipases
  • Potassium