Abstract
Interleukin-2 (IL-2) and IL-15 exert similar biological actions, which largely reflect the fact that their receptors share common β and γ subunits; in contrast, distinct α subunits are required for high-affinity binding of either cytokine to a heterotrimeric receptor-complex. Human neutrophils are known to express both the β and γ subunits of the IL-2/IL- 15 receptor complex, and we now report that they also constitutively express messenger RNA transcripts encoding the IL-15 receptor α chain, suggesting that they possess functional, heterotrimeric IL-15 receptors. Accordingly, we show that in neutrophils, IL-15 elicits several functional responses. In particular, neutrophils synthesize and release IL-8 in response to IL-15, but not to IL-2. Moreover, a nuclear factor-κB (NF-κB) DNA-binding activity was enhanced in nuclear extracts of IL-15-treated neutrophils, which could be super-shifted by antibodies to p50 or RelA. Again, no detectable effect of IL-2 was observed on this response. In peripheral blood lymphocytes (PBL), however, both IL-2 and IL-15 were potent inducers of NF-κB activation. Conversely, neither IL-15 nor IL-2 elicited the formation of activator protein-1 (AP-1) DNA-binding complexes in neutrophils, even though both cytokines were found to activate these DNA-binding activities in PBL. Collectively, these observations establish neutrophils as a useful cellular model to discriminate between the actions of IL-15 and IL-2. More importantly, this is the first demonstration that IL-15 has the ability to induce NF-κB and AP-1 activation, which further emphasizes the potential relevance of this newly discovered cytokine to immune and inflammatory processes.
| Original language | English |
|---|---|
| Pages (from-to) | 4828-4835 |
| Number of pages | 8 |
| Journal | Blood |
| Volume | 92 |
| Issue number | 12 |
| Publication status | Published - Dec 15 1998 |
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ASJC Scopus subject areas
- Hematology
Cite this
Interleukin-15 (IL-15) induces NF-κB activation and IL-8 production in human neutrophils. / McDonald, Patrick P.; Russo, Maria Pia; Ferrini, Silvano; Cassatella, Marco A.
In: Blood, Vol. 92, No. 12, 15.12.1998, p. 4828-4835.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - Interleukin-15 (IL-15) induces NF-κB activation and IL-8 production in human neutrophils
AU - McDonald, Patrick P.
AU - Russo, Maria Pia
AU - Ferrini, Silvano
AU - Cassatella, Marco A.
PY - 1998/12/15
Y1 - 1998/12/15
N2 - Interleukin-2 (IL-2) and IL-15 exert similar biological actions, which largely reflect the fact that their receptors share common β and γ subunits; in contrast, distinct α subunits are required for high-affinity binding of either cytokine to a heterotrimeric receptor-complex. Human neutrophils are known to express both the β and γ subunits of the IL-2/IL- 15 receptor complex, and we now report that they also constitutively express messenger RNA transcripts encoding the IL-15 receptor α chain, suggesting that they possess functional, heterotrimeric IL-15 receptors. Accordingly, we show that in neutrophils, IL-15 elicits several functional responses. In particular, neutrophils synthesize and release IL-8 in response to IL-15, but not to IL-2. Moreover, a nuclear factor-κB (NF-κB) DNA-binding activity was enhanced in nuclear extracts of IL-15-treated neutrophils, which could be super-shifted by antibodies to p50 or RelA. Again, no detectable effect of IL-2 was observed on this response. In peripheral blood lymphocytes (PBL), however, both IL-2 and IL-15 were potent inducers of NF-κB activation. Conversely, neither IL-15 nor IL-2 elicited the formation of activator protein-1 (AP-1) DNA-binding complexes in neutrophils, even though both cytokines were found to activate these DNA-binding activities in PBL. Collectively, these observations establish neutrophils as a useful cellular model to discriminate between the actions of IL-15 and IL-2. More importantly, this is the first demonstration that IL-15 has the ability to induce NF-κB and AP-1 activation, which further emphasizes the potential relevance of this newly discovered cytokine to immune and inflammatory processes.
AB - Interleukin-2 (IL-2) and IL-15 exert similar biological actions, which largely reflect the fact that their receptors share common β and γ subunits; in contrast, distinct α subunits are required for high-affinity binding of either cytokine to a heterotrimeric receptor-complex. Human neutrophils are known to express both the β and γ subunits of the IL-2/IL- 15 receptor complex, and we now report that they also constitutively express messenger RNA transcripts encoding the IL-15 receptor α chain, suggesting that they possess functional, heterotrimeric IL-15 receptors. Accordingly, we show that in neutrophils, IL-15 elicits several functional responses. In particular, neutrophils synthesize and release IL-8 in response to IL-15, but not to IL-2. Moreover, a nuclear factor-κB (NF-κB) DNA-binding activity was enhanced in nuclear extracts of IL-15-treated neutrophils, which could be super-shifted by antibodies to p50 or RelA. Again, no detectable effect of IL-2 was observed on this response. In peripheral blood lymphocytes (PBL), however, both IL-2 and IL-15 were potent inducers of NF-κB activation. Conversely, neither IL-15 nor IL-2 elicited the formation of activator protein-1 (AP-1) DNA-binding complexes in neutrophils, even though both cytokines were found to activate these DNA-binding activities in PBL. Collectively, these observations establish neutrophils as a useful cellular model to discriminate between the actions of IL-15 and IL-2. More importantly, this is the first demonstration that IL-15 has the ability to induce NF-κB and AP-1 activation, which further emphasizes the potential relevance of this newly discovered cytokine to immune and inflammatory processes.
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M3 - Article
VL - 92
SP - 4828
EP - 4835
JO - Blood
JF - Blood
SN - 0006-4971
IS - 12
ER -