关键词： Immunosuppression Interleukin-10 (IL-10) Interleukin-4 (IL-4) Natural killer (NK) cell Signaling Transcription regulation Transforming growth factor beta (TGF-β)

Mesh ： Anthracenes / pharmacology Cell Line Cell Proliferation Cyclic AMP Response Element-Binding Protein / genetics Humans Interferon-gamma / biosynthesis metabolism Interleukin-10 / immunology pharmacology Interleukin-2 / immunology Interleukin-4 / immunology pharmacology Intracellular Signaling Peptides and Proteins / immunology JNK Mitogen-Activated Protein Kinases / antagonists & inhibitors Killer Cells, Natural / drug effects immunology Lymphocyte Activation / immunology MAP Kinase Kinase 1 / antagonists & inhibitors Neoplasms / immunology Phosphorylation / drug effects Promoter Regions, Genetic / immunology Protein-Tyrosine Kinases / immunology Proto-Oncogene Proteins c-myb / genetics Proto-Oncogene Proteins c-myc / biosynthesis Receptors, Androgen / genetics Signal Transduction / drug effects immunology Syk Kinase Transcription Factor AP-1 / genetics Transforming Growth Factor beta / immunology pharmacology Tumor Escape / immunology

来  源：   DOI：10.1016/j.cellimm.2014.05.001   PDF(Sci-hub)

Abstract：
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-β, IL-10, and IL-4 on primary NK cells, and it was demonstrated that (1) TGF-β most potently inhibited the overall function of NK cells. (2) It appears that TGF-β 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-β treatment. Interestingly, TGF-β 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-β in modulating NK cell functions.
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