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Albrecht U Yang X Asselta R Keitel V Tenchini ML Ludwig S Heinrich PC Häussinger D Schaper F Bode JG 《Cellular signalling》2007,19(9):1866-1878
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IL-21 in synergy with IL-15 or IL-18 enhances IFN-gamma production in human NK and T cells 总被引:16,自引:0,他引:16
Strengell M Matikainen S Sirén J Lehtonen A Foster D Julkunen I Sareneva T 《Journal of immunology (Baltimore, Md. : 1950)》2003,170(11):5464-5469
NK and T cell-derived IFN-gamma is a key cytokine that stimulates innate immune responses and directs adaptive T cell response toward Th1 type. IL-15, IL-18, and IL-21 have significant roles as activators of NK and T cell functions. We have previously shown that IL-15 and IL-21 induce the expression of IFN-gamma, T-bet, IL-12R beta 2, and IL-18R genes both in NK and T cells. Now we have studied the effect of IL-15, IL-18, and IL-21 on IFN-gamma gene expression in more detail in human NK and T cells. IL-15 clearly activated IFN-gamma mRNA expression and protein production in both cell types. IL-18 and IL-21 enhanced IL-15-induced IFN-gamma gene expression. IL-18 or IL-21 alone induced a modest expression of the IFN-gamma gene but a combination of IL-21 and IL-18 efficiently up-regulated IFN-gamma production. We also show that IL-15 activated the binding of STAT1, STAT3, STAT4, and STAT5 to the regulatory sites of the IFN-gamma gene. Similarly, IL-21 induced the binding of STAT1, STAT3, and STAT4 to these elements. IL-15- and IL-21-induced STAT1 and STAT4 activation was verified by immunoprecipitation with anti-phosphotyrosine Abs followed by Western blotting with anti-STAT1 and anti-STAT4 Abs. IL-18 was not able to induce the binding of STATs to IFN-gamma gene regulatory sites. IL-18, however, activated the binding of NF-kappa B to the IFN-gamma promoter NF-kappa B site. Our results suggest that both IL-15 and IL-21 have an important role in activating the NK cell-associated innate immune response. 相似文献
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Haller D Holt L Kim SC Schwabe RF Sartor RB Jobin C 《The Journal of biological chemistry》2003,278(26):23851-23860
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