Published online before print February 24, 2004
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
INRS-Institut Armand-Frappier, Université du Québec, Pointe-Claire, Canada
1 Correspondence: INRS-Institut Armand-Frappier, 245 boul. Hymus, Pointe-Claire (PQ), Canada, H9R 1G6. E-mail: denis.girard{at}inrs-iaf.uquebec.ca
Interleukin-15 (IL-15) induces the de novo protein synthesis of intracellular polypeptides and delays neutrophil apoptosis by a mechanism that is still unclear. Herein, we investigated the potential antiapoptotic role of newly synthesized proteins released into the external milieu in IL-15-induced neutrophils. We found that IL-15 induces the de novo synthesis of an 
23-kDa protein, representing the predominant protein detected in the milieu, and identified it as IL-1 receptor antagonist (IL-1Ra) by Western blot and immunoprecipitation. We quantified IL-1Ra, IL-1
, and IL-1ß concentrations by enzyme-linked immunosorbent assay in intracellular and extracellular fractions from IL-15-induced neutrophils and found that IL-15 does not increase IL-1 or IL-1ß production but induces IL-1Ra release. Also, we demonstrated that IL-1Ra does not modulate apoptosis, even at a concentration 250 times greater than that measured in the external milieu. In contrast to granulocyte macrophage-colony stimulating factor, the supernatant harvested from IL-15-induced neutrophils was devoid of antiapoptotic activity. Addition of cycloheximide demonstrates that IL-15 delays apoptosis via de novo synthesis of intracellular proteins and that it increases myeloid cell differentiation factor-1 stability. We demonstrated also that IL-15 decreases the activity of caspase-3 and caspase-8, resulting in an inhibition of vimentin cleavage. Our results indicate that IL-15 can activate an anti-inflammatory loop, based on its ability to induce the synthesis of IL-1Ra by neutrophils. We conclude that IL-15 delays human neutrophil apoptosis by intracellular events and not via extracellular factors.
Key Words: cytokine • inflammation • de novo protein synthesis
This article has been cited by other articles:
 |
|
 |
|
  S. Conus, R. Perozzo, T. Reinheckel, C. Peters, L. Scapozza, S. Yousefi, and H.-U. Simon Caspase-8 is activated by cathepsin D initiating neutrophil apoptosis during the resolution of inflammation J. Exp. Med., March 17, 2008; 205(3): 685 - 698. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 C. Ratthe, M. Pelletier, S. Chiasson, and D. Girard Molecular mechanisms involved in interleukin-4-induced human neutrophils: expression and regulation of suppressor of cytokine signaling J. Leukoc. Biol., May 1, 2007; 81(5): 1287 - 1296. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 A. Wimmer, S. K. Khaldoyanidi, M. Judex, N. Serobyan, R. G. DiScipio, and I. U. Schraufstatter CCL18/PARC stimulates hematopoiesis in long-term bone marrow cultures indirectly through its effect on monocytes Blood, December 1, 2006; 108(12): 3722 - 3729. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
E. Moisan and D. Girard Cell surface expression of intermediate filament proteins vimentin and lamin B1 in human neutrophil spontaneous apoptosis J. Leukoc. Biol., March 1, 2006; 79(3): 489 - 498. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 K.-S. Choi, J. T. Park, and J. S. Dumler Anaplasma phagocytophilum Delay of Neutrophil Apoptosis through the p38 Mitogen-Activated Protein Kinase Signal Pathway Infect. Immun., December 1, 2005; 73(12): 8209 - 8218. [Abstract] [Full Text] [PDF]
|
|
