IL-12 and IL-15 induce activation of nuclear PLCbeta in human natural killer cells.
Nuclear phosphoinositide breakdown mediated by nuclear PLCbeta phosphorylation is a downstream effect of IL-2 stimulation in primary human NK cells that is involved in the proliferative response to IL-2. Here we investigated whether the nuclear phosphoinositide turnover in NK cells is a response confined to IL-2, or rather represents a more general mechanism of nuclear signalling linked to the proliferative response of NK cells to activatory cytokines. We therefore focused on IL-12 and IL-15-induced nuclear events in primary human NK cells. Our results show that IL-12 and IL-15 activate nuclear PLCbeta1 in NK cells, with delayed kinetics as compared to IL-2. The nuclear PLC activation induced by the cytokines could be blocked by the MEK-1 inhibitor PD 98059, suggesting its dependence upon MAPKinase activation. Our conclusion is that the three cytokines that activate NK cells and that bind partially similar (IL-2, IL-15) or different surface receptors (IL-12), all induce activation of PLCbeta1 in the nucleus of NK cells via MAPKinase. Thus, the activation of nuclear PLCbeta1 appears as a physiologically relevant general mechanism of response to cytokine stimulation in human natural killer cells.
Ponti
Cristina
C
Department of Anatomical Sciences, Cellular Signalling Laboratory, University of Bologna, I-40126 Bologna, Italy. crisponti@hotmail.com
Falconi
Mirella
M
Billi
Anna Maria
AM
Faenza
Irene
I
Castorina
Sergio
S
Caimi
Luigi
L
Cacchioli
Antonio
A
Cocco
Lucio
L
Vitale
Marco
M
D015153:Blotting, Western; D002467:Cell Nucleus; D002478:Cells, Cultured; D004305:Dose-Response Relationship, Drug; D004789:Enzyme Activation; D006801:Humans; D018664:Interleukin-12 / Q000494:pharmacology*; D019409:Interleukin-15 / Q000494:pharmacology*; D007527:Isoenzymes / Q000378:metabolism*; D007694:Killer Cells, Natural / Q000187:drug effects* / Q000201:enzymology; D007700:Kinetics; D054799:Phospholipase C beta; D010738:Type C Phospholipases / Q000378:metabolism*
D019409:Interleukin-15; D007527:Isoenzymes; D018664:Interleukin-12; D010738:Type C Phospholipases; D054799:Phospholipase C beta