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

FEBS Letters

Gardella, Stefania²  Rubartelli, Anna²  Poggi, Alessandro¹  Zocchi, M.Raffaella²  Andrei, Cristina² 

[1] Laboratory of Immunopathology, National Institute for Cancer Research and Advanced Biotechnology Center, 16132 Genova, Italy;Group of Protein Biology, National Institute for Cancer Research, Largo Rosanna Benzi 10, 16132 Genova, Italy

关键词: Interleukin-18;    Dendritic cell;    Degradation;    Leaderless secretion;    Secretory lysosome;    Calcium channel;    DC;    dendritic cell;    HRP;    horseradish peroxidase;    ICE;    IL-1β-converting enzyme;    IL;    interleukin;    LPS;    lipopolysaccharide;    NFD;    nifedipine;    PBMC;    peripheral blood mononuclear cells;    PNS;    post-nuclear supernatant;    TCA;    trichloroacetic acid;   

DOI  :  10.1016/S0014-5793(00)02015-9

学科分类：生物化学/生物物理

来源: John Wiley & Sons Ltd.

【 摘 要 】

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.

【 授权许可】

Unknown