title: NK-active cytokines IL-2, IL-12, and IL-15 selectively modulate specific protein kinase C (PKC) isoforms in primary human NK cells.
abstract: Natural killer (NK) cell function is largely modulated by growth factors and cytokines. In particular, interleukin (IL)-2, IL-12, and IL-15 have major effects on the proliferative and cytotoxic activities of NK cells against tumor and virus-infected cells. It is thought that the members of the protein kinase C (PKC) family of serine/threonine kinases play an important role in mediating the pleiotropic effects of cytokines on their target cells. We have investigated the downstream effects generated in purified human NK cells by IL-2, IL-12, and IL-15 on PKCalpha and PKCepsilon--a canonical and a novel isoform of PKC, respectively. By means of Western blotting, PKC activity assays, and immunofluorescence performed on highly purified preparations of primary human NK cells, we demonstrate that: 1) the three cytokines have similar effects on PKCalpha and PKCepsilon activities; 2) whereas PKCepsilon activity is induced by cytokine stimulation, PKCalpha activity is inhibited; and 3) both the induction of PKCepsilon and the inhibition of PKCalpha functional activity are relatively early events in NK cells, while longer cytokine stimulations do not generate significant variations in enzyme activity, suggesting that the activation of both the canonical and novel isoforms of PKC are events required in the early phases of cytokine-induced NK cell stimulation.
authors.affiliation: Institute of Human Anatomy, University of Parma, Ospedale Maggiore, Parma, Italy. vitale@unipr.it
authors.forename: Marco
authors.initials: M
authors.lastname: Vitale
authors.forename: Alessandra
authors.initials: A
authors.lastname: Bassini
authors.forename: Paola
authors.initials: P
authors.lastname: Secchiero
authors.forename: Prisco
authors.initials: P
authors.lastname: Mirandola
authors.forename: Cristina
authors.initials: C
authors.lastname: Ponti
authors.forename: Loris
authors.initials: L
authors.lastname: Zamai
authors.forename: Adriana R
authors.initials: AR
authors.lastname: Mariani
authors.forename: Mirella
authors.initials: M
authors.lastname: Falconi
authors.forename: Giacomo
authors.initials: G
authors.lastname: Azzali
mesh_terms: D015153:Blotting, Western; D002478:Cells, Cultured; D004790:Enzyme Induction; D019084:Fluorescent Antibody Technique, Indirect; D006801:Humans; D018664:Interleukin-12 / Q000494:pharmacology; D019409:Interleukin-15 / Q000494:pharmacology; D007376:Interleukin-2 / Q000494:pharmacology; D007378:Interleukins / Q000494:pharmacology*; D007527:Isoenzymes / Q000096:biosynthesis*; D007694:Killer Cells, Natural / Q000187:drug effects* / Q000201:enzymology; D011493:Protein Kinase C / Q000096:biosynthesis*; D051571:Protein Kinase C-alpha; D051744:Protein Kinase C-epsilon
chemical_list: D019409:Interleukin-15; D007376:Interleukin-2; D007378:Interleukins; D007527:Isoenzymes; D018664:Interleukin-12; C496628:PRKCA protein, human; C497255:PRKCE protein, human; D011493:Protein Kinase C; D051571:Protein Kinase C-alpha; D051744:Protein Kinase C-epsilon