Control of interleukin-18 secretion by dendritic cells: role of calcium influxes

FEBS Lett. 2000 Sep 22;481(3):245-8. doi: 10.1016/s0014-5793(00)02015-9.


Here we show that dendritic cells accumulate the precursor form of the leaderless secretory protein interleukin-18 (pro-interleukin-18) in the cell cytosol and in organelles co-fractionating with endolysosomes. Upon antigen specific contact with T lymphocytes, particulated pro-interleukin-18 decreases rapidly, and the cytokine appears extracellularly, suggesting that exocytosis of pro-interleukin-18-containing organelles is induced. Exocytosis of secretory lysosomes is modulated by calcium: in agreement with this, calcium influx results in secretion of pro-interleukin-18. In turn, pro-interleukin-18 secretion induced by T cells is prevented by the calcium channel blocker nifedipine. Our results demonstrate a novel, calcium-mediated mechanism of post-translational regulation of secretion for interleukin-18, that allows a fast release of the cytokine.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Calcium / metabolism
  • Calcium / physiology*
  • Calcium Signaling / immunology
  • Cell Communication / immunology
  • Dendritic Cells / immunology
  • Dendritic Cells / metabolism*
  • Extracellular Space / physiology
  • Humans
  • Interleukin-18 / biosynthesis
  • Interleukin-18 / metabolism*
  • Intracellular Fluid / immunology
  • Intracellular Fluid / metabolism
  • Lysosomes / metabolism
  • Protein Precursors / biosynthesis
  • Protein Precursors / metabolism
  • T-Lymphocytes / immunology
  • T-Lymphocytes / metabolism


  • Interleukin-18
  • Protein Precursors
  • Calcium