A comparative study of the effects of inhibitory cytokines on human natural killer cells and the mechanistic features of transforming growth factor-beta

The major factors and mechanisms by which natural killer (NK) cells are inhibited in cancer patients have not yet been well defined. In this study, we conducted a comparative analysis of the effects of TGF-beta, IL-10, and IL-4 on primary NI( cells, and it was demonstrated that (1) TGF-beta most potently inhibited the overall function of NK cells. (2) It appears that TGF-beta reduced the tyrosine phosphorylation of Syk and the expression of c-myc. (3) It was also found that the IL-2-induced promoter-binding activities of C-myb, AP-1, CREB, and AR were also completely suppressed upon TGF-beta treatment. Interestingly, TGF-beta also completely suppressed other transcription factors, which are constitutively activated. Among these factors, we further confirmed roles of AP-1 in NK-92 cell activation through c-jun and MEK1 inhibitor assay. Our study provides insight into the effects of TGF-beta in modulating NK cell functions. (C) 2014 Elsevier Inc. All rights reserved.