Interleukin-15 (IL-15) induces NF-κB activation and IL-8 production in human neutrophils

Patrick P. McDonald, Maria Pia Russo, Silvano Ferrini, Marco A. Cassatella

Research output: Contribution to journalArticle

103 Citations (Scopus)

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 languageEnglish
Pages (from-to)4828-4835
Number of pages8
JournalBlood
Volume92
Issue number12
Publication statusPublished - Dec 15 1998

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Interleukin-15
Interleukin-8
Neutrophils
Interleukin-2
Chemical activation
Interleukin-15 Receptors
Lymphocytes
Transcription Factor AP-1
Cytokines
DNA
Blood
Demonstrations
Messenger RNA
Antibodies

ASJC Scopus subject areas

  • Hematology

Cite this

McDonald, P. P., Russo, M. P., Ferrini, S., & Cassatella, M. A. (1998). Interleukin-15 (IL-15) induces NF-κB activation and IL-8 production in human neutrophils. Blood, 92(12), 4828-4835.

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 journalArticle

McDonald, PP, Russo, MP, Ferrini, S & Cassatella, MA 1998, 'Interleukin-15 (IL-15) induces NF-κB activation and IL-8 production in human neutrophils', Blood, vol. 92, no. 12, pp. 4828-4835.
McDonald PP, Russo MP, Ferrini S, Cassatella MA. Interleukin-15 (IL-15) induces NF-κB activation and IL-8 production in human neutrophils. Blood. 1998 Dec 15;92(12):4828-4835.
McDonald, Patrick P. ; Russo, Maria Pia ; Ferrini, Silvano ; Cassatella, Marco A. / Interleukin-15 (IL-15) induces NF-κB activation and IL-8 production in human neutrophils. In: Blood. 1998 ; Vol. 92, No. 12. pp. 4828-4835.
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