Gene expression and secretion of cytokines and cytokine receptors from highly purified CD56+ natural killer cells stimulated with interleukin-2, interleukin-7 and interleukin-12.
Interleukin (IL)-2 IL-7 and IL-12 stimulate the generation of lymphokine-activated killer activity and proliferation in natural killer (NK) cells by different mechanisms. In this study, we have compared the ability of IL-2, IL-7 and IL-12 to induce expression of cytokines and cytokine receptors both at the gene and protein level. IL-2 and IL-12 stimulated the CD56+ NK cells to release significant amounts of soluble p55 and p75 tumor necrosis factor receptor (TNFR), whereas less amounts of soluble TNFR were detected in IL-7-stimulated cultures. The p55 and p75 TNFR mRNA were expressed in resting NK cells, and no further induction was observed after cytokine-stimulation. Compared to the effects of IL-2, IL-7 induced lower, but substantial levels of granulocyte-macrophage colony-stimulating factor (GM-CSF) mRNA, and IL-7 was a more potent GM-CSF-inducing stimulus than IL-12. IL-12 induced higher levels of interferon-gamma (IFN-gamma) mRNA than did IL-2, and IL-7 only weakly influenced the IFN-gamma expression. In accordance with the mRNA studies, IL-7 induced the secretion of high amounts of GM-CSF and no or low levels of IFN-gamma, whereas high amounts of IFN-gamma and low levels of GM-CSF were detected in supernatants from IL-12-stimulated NK cells. In conclusion, IL-2, IL-7 and IL-12 differentially regulate expression of cytokines and cytokine receptors both at the gene and protein level.
Naume
B
B
Institute of Cancer Research, University of Trondheim, Norway.
Johnsen
A C
AC
Espevik
T
T
Sundan
A
A
D000818:Animals; D015703:Antigens, CD / Q000032:analysis*; D000945:Antigens, Differentiation, T-Lymphocyte / Q000032:analysis*; D001483:Base Sequence; D019002:CD56 Antigen; D016207:Cytokines / Q000096:biosynthesis* / Q000235:genetics; D015870:Gene Expression / Q000187:drug effects; D006801:Humans; D018664:Interleukin-12; D007376:Interleukin-2 / Q000494:pharmacology; D015851:Interleukin-7 / Q000494:pharmacology; D007378:Interleukins / Q000494:pharmacology*; D007694:Killer Cells, Natural / Q000187:drug effects / Q000276:immunology* / Q000378:metabolism; D008969:Molecular Sequence Data; D011956:Receptors, Cell Surface / Q000096:biosynthesis* / Q000235:genetics; D015375:Receptors, Interleukin-2 / Q000096:biosynthesis* / Q000235:genetics; D018124:Receptors, Tumor Necrosis Factor
D015703:Antigens, CD; D000945:Antigens, Differentiation, T-Lymphocyte; D019002:CD56 Antigen; D016207:Cytokines; D007376:Interleukin-2; D015851:Interleukin-7; D007378:Interleukins; D011956:Receptors, Cell Surface; D015375:Receptors, Interleukin-2; D018124:Receptors, Tumor Necrosis Factor; D018664:Interleukin-12