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Titolo:
Interleukin-2 enhances the response of natural killer cells to interleukin-12 through up-regulation of the interleukin-12 receptor and STAT4
Autore:
Wang, KS; Frank, DA; Ritz, J;
Indirizzi:
Dana Farber Canc Inst, Ctr Hematol Oncol, Dept Adult Oncol, Boston, MA 02115 USA Dana Farber Canc Inst Boston MA USA 02115 ult Oncol, Boston, MA 02115 USA Harvard Univ, Brigham & Womens Hosp, Dept Med, Boston, MA 02115 USA Harvard Univ Boston MA USA 02115 ens Hosp, Dept Med, Boston, MA 02115 USA
Titolo Testata:
BLOOD
fascicolo: 10, volume: 95, anno: 2000,
pagine: 3183 - 3190
SICI:
0006-4971(20000515)95:10<3183:IETRON>2.0.ZU;2-6
Fonte:
ISI
Lingua:
ENG
Soggetto:
STIMULATORY FACTOR NKSF; IFN-GAMMA PRODUCTION; T-CELLS; TYROSINE PHOSPHORYLATION; HUMAN-LYMPHOCYTES; INTERFERON-GAMMA; TH2 CELLS; SELECTIVE EXPRESSION; RECOMBINANT IL-12; BETA-CHAIN;
Tipo documento:
Article
Natura:
Periodico
Settore Disciplinare:
Clinical Medicine
Life Sciences
Citazioni:
51
Recensione:
Indirizzi per estratti:
Indirizzo: Ritz, J Dana Farber Canc Inst, Ctr Hematol Oncol, Dept Adult Oncol, 44 Binney St, Boston, MA 02115 USA Dana Farber Canc Inst 44 Binney St Boston MA USA 02115 A 02115 USA
Citazione:
K.S. Wang et al., "Interleukin-2 enhances the response of natural killer cells to interleukin-12 through up-regulation of the interleukin-12 receptor and STAT4", BLOOD, 95(10), 2000, pp. 3183-3190

Abstract

Interleukin (IL)-12 plays a critical role in modulating the activities of natural killer (NK) cells and T lymphocytes, In animal models, IL-12 has potent antitumor effects that are likely mediated by its ability to enhance the cytotoxic activity of NK cells and cytotoxic T lymphocytes, and to induce the production of interferon (IFN)-gamma by NK and T cells. In addition to IL-12, NK cells are responsive to IL-2, and may mediate some of the antitumor effects of IL-2, In this study, we examine the interaction between IL-2 and the signaling events induced by IL-12 in NK cells. We find that IL-2 not only up-regulates the expression of IL-12R beta 1 and IL-12R beta 2, italso plays an important role in up-regulating and maintaining the expression of STAT4, a critical STAT protein involved in IL-12 signaling in NK cells, In contrast to the effects of IL-2 alone, expression of IL-12 receptors and STAT4 are unaffected or decreased by IL-12 or the combination of IL-2 and IL-12. Through expression of high levels of IL-12 receptors and STAT4, IL-2-primed NK cells show enhanced functional responses to IL-12 as measuredby IFN-gamma production and the killing of target cells. NK cells from cancer patients who received low-dose IL-2 treatment also exhibited increased expression of IL-12 receptor chains, suggesting that IL-2 may enhance the response to IL-12 in vivo. These findings provide a molecular framework to understand the interaction between IL-2 and IL-12 in NK cells, and suggest strategies for improving the effectiveness of these cytokines in the immunotherapy of cancer, (C) 2000 by The American Society of Hematology.

ASDD Area Sistemi Dipartimentali e Documentali, Università di Bologna, Catalogo delle riviste ed altri periodici
Documento generato il 05/04/20 alle ore 00:08:20