Journal
FEBS LETTERS
Volume 532, Issue 1-2, Pages 164-170Publisher
WILEY
DOI: 10.1016/S0014-5793(02)03668-2
Keywords
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
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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. (C) 2002 Federation of European Biochemical Societies. Published by Elsevier Science B.V. All rights reserved.
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