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Interleukin‐15 delays human neutrophil apoptosis by intracellular events and not via extracellular factors: role of Mcl‐1 and decreased activity of caspase‐3 and caspase‐8
Author(s) -
Bouchard Amélie,
Ratthé Claude,
Girard Denis
Publication year - 2004
Publication title -
journal of leukocyte biology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.819
H-Index - 191
eISSN - 1938-3673
pISSN - 0741-5400
DOI - 10.1189/jlb.1103585
Subject(s) - cycloheximide , biology , apoptosis , intracellular , extracellular , microbiology and biotechnology , interleukin , caspase , neutrophil extracellular traps , cytokine , programmed cell death , inflammation , protein biosynthesis , immunology , biochemistry
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‐1α, and IL‐1β 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‐1α or IL‐1β production but induces IL‐1Ra release. Also, we demonstrated that IL‐1Ra does not modulate apoptosis, een 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.