TY - JOUR
T1 - Control of interleukin-18 secretion by dendritic cells
T2 - Role of calcium influxes
AU - Gardella, Stefania
AU - Andrei, Cristina
AU - Poggi, Alessandro
AU - Zocchi, M. Raffaella
AU - Rubartelli, Anna
PY - 2000/9/22
Y1 - 2000/9/22
N2 - 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. (C) 2000 Federation of European Biochemical Societies.
AB - 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. (C) 2000 Federation of European Biochemical Societies.
KW - Calcium channel
KW - Degradation
KW - Dendritic cell
KW - Interleukin-18
KW - Leaderless secretion
KW - Secretory lysosome
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U2 - 10.1016/S0014-5793(00)02015-9
DO - 10.1016/S0014-5793(00)02015-9
M3 - Article
C2 - 11007972
AN - SCOPUS:0034703465
VL - 481
SP - 245
EP - 248
JO - FEBS Letters
JF - FEBS Letters
SN - 0014-5793
IS - 3
ER -