Control of interleukin-18 secretion by dendritic cells: role of calcium influxes.
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.
Gardella
S
S
Group of Protein Biology, National Institute for Cancer Research, Largo Rosanna Benzi 10, 16132, Genova, Italy.
Andrei
C
C
Poggi
A
A
Zocchi
M R
MR
Rubartelli
A
A
D002118:Calcium / Q000378:metabolism / Q000502:physiology*; D020013:Calcium Signaling / Q000276:immunology; D002450:Cell Communication / Q000276:immunology; D003713:Dendritic Cells / Q000276:immunology / Q000378:metabolism*; D005110:Extracellular Space / Q000502:physiology; D006801:Humans; D020382:Interleukin-18 / Q000096:biosynthesis / Q000378:metabolism*; D007424:Intracellular Fluid / Q000276:immunology / Q000378:metabolism; D008247:Lysosomes / Q000378:metabolism; D011498:Protein Precursors / Q000096:biosynthesis / Q000378:metabolism; D013601:T-Lymphocytes / Q000276:immunology / Q000378:metabolism
D020382:Interleukin-18; D011498:Protein Precursors; D002118:Calcium