Pelletier, Martin; Ratthé, Claude et Girard, Denis 
ORCID: https://orcid.org/0000-0002-3342-5027
(2002).
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
, vol. 532
, nº 1-2.
pp. 164-170.
DOI: 10.1016/s0014-5793(02)03668-2.
Résumé
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.
| Type de document: | Article |
|---|---|
| Mots-clés libres: | 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 |
| Centre: | Centre INRS-Institut Armand Frappier |
| Date de dépôt: | 04 mars 2025 15:33 |
| Dernière modification: | 04 mars 2025 15:33 |
| URI: | https://espace.inrs.ca/id/eprint/15051 |
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