Mechanisms involved in interleukin‐15‐induced suppression of human neutrophil apoptosis: role of the anti‐apoptotic Mcl‐1 protein and several kinases including Janus kinase‐2, p38 mitogen‐activated protein kinase and extracellular signal‐regulated kinases‐1/2

FEBS Letters

Pelletier, Martin¹  Girard, Denis¹  Ratthé, Claude¹ 

[1]INRS-Institut Armand-Frappier/Santé humaine, Université du Québec, 245 boul. Hymus, Pointe-Claire, QC, Canada H9R 1G6

关键词: Inflammation;    Cytokine;    Anti-apoptotic;    Mcl-1;    Janus kinase;    Signal transducer and activator of transcription;    p38 mitogen-activated protein kinase;    Extracellular signal-regulated kinase-1/2;    IL-15;    interleukin-15;    VAA-I;    Viscum album agglutinin-I;    GM-CSF;    granulocyte macrophage-colony-stimulating factor;    Jak;    Janus kinase;    STAT;    signal transducer and activator of transcription;    MAPK;    mitogen-activated protein kinase;    ERK;    extracellular signal-regulated kinase;   

DOI  :  10.1016/S0014-5793(02)03668-2

学科分类：生物化学/生物物理

来源: John Wiley & Sons Ltd.

【 摘 要 】

Interleukin-15 (IL-15) is a pro-inflammatory cytokine known as a general inhibitor of apoptosis, which possesses potential therapeutic properties. Although IL-15 was previously found to be a human neutrophil agonist, its mode of action remains unknown. Herein, we were interested in elucidating the mechanisms by which it delays neutrophil apoptosis. IL-15 was found to induce tyrosine phosphorylation events and to prevent loss of the anti-apoptotic Mcl-1 protein expression. Using different signal transduction inhibitors, we found that Janus kinase (Jak)-2, Jak-3, p38 mitogen-activated protein kinase (MAPK) and extracellular signal-regulated kinase (ERK), but not G proteins, are involved in IL-15-induced suppression of apoptosis. Furthermore, we found that IL-15 activates Jak-2, p38 MAPK and ERK-1/2, but, unlike granulocyte macrophage-colony-stimulating factor (GM-CSF), it does not activate signal transducer and activator of transcription (STAT)-5a/b. We conclude that IL-15 delays neutrophil apoptosis via several pathways, and that Mcl-1 and several kinases contribute to this. We also conclude that, unlike GM-CSF, IL-15 does not activate the Jak-2/STAT-5 pathway found to be important in neutrophil signaling.

【 授权许可】

Unknown