Interleukin-15 (IL-15) induces NF-kappaB activation and IL-8 production in human neutrophils.
Interleukin-2 (IL-2) and IL-15 exert similar biological actions, which largely reflect the fact that their receptors share common beta and gamma subunits; in contrast, distinct subunits are required for high-affinity binding of either cytokine to a heterotrimeric receptor complex. Human neutrophils are known to express both the beta and gamma 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 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-kappaB (NF-kappaB) DNA-binding activity was enhanced in nuclear extracts of IL-15-treated neutrophils, which could be supershifted 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-kappaB 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-kappaB and AP-1 activation, which further emphasizes the potential relevance of this newly discovered cytokine to immune and inflammatory processes.
McDonald
P P
PP
Department of General Pathology, University of Verona, Verona, Italy. mdonaldp@njc.org
Russo
M P
MP
Ferrini
S
S
Cassatella
M A
MA
D015870:Gene Expression; D006801:Humans; D019409:Interleukin-15 / Q000494:pharmacology*; D007376:Interleukin-2 / Q000494:pharmacology; D016209:Interleukin-8 / Q000096:biosynthesis*; D008214:Lymphocytes / Q000187:drug effects / Q000378:metabolism; D016328:NF-kappa B / Q000378:metabolism*; D009504:Neutrophils / Q000187:drug effects* / Q000378:metabolism*; D011485:Protein Binding; D012333:RNA, Messenger / Q000032:analysis; D053647:Receptors, Interleukin-15; D015375:Receptors, Interleukin-2 / Q000235:genetics*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D018808:Transcription Factor AP-1 / Q000378:metabolism
C508024:IL15RA protein, human; D019409:Interleukin-15; D007376:Interleukin-2; D016209:Interleukin-8; D016328:NF-kappa B; D012333:RNA, Messenger; D053647:Receptors, Interleukin-15; D015375:Receptors, Interleukin-2; D018808:Transcription Factor AP-1