title: A comparative study of the effects of inhibitory cytokines on human natural killer cells and the mechanistic features of transforming growth factor-beta.
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.
authors.affiliation: Department of Microbiology and Brain Korea 21 PLUS project for Medical science, Yonsei University College of Medicine, 50 Yonsei-ro, Seodaemun-gu, Seoul 120-752, Republic of Korea.
authors.forename: Hae Mi
authors.initials: HM
authors.lastname: Lee
authors.affiliation: Department of Biochemistry and Molecular Biology, Yonsei University College of Medicine, 50 Yonsei-ro, Seodaemun-gu, Seoul 120-752, Republic of Korea.
authors.forename: Kyung-Sup
authors.initials: KS
authors.lastname: Kim
authors.affiliation: Department of Microbiology and Brain Korea 21 PLUS project for Medical science, Yonsei University College of Medicine, 50 Yonsei-ro, Seodaemun-gu, Seoul 120-752, Republic of Korea. Electronic address: jkim63@yuhs.ac.
authors.forename: Jongsun
authors.initials: J
authors.lastname: Kim
mesh_terms: D000873:Anthracenes / Q000494:pharmacology; D002460:Cell Line; D049109:Cell Proliferation; D017362:Cyclic AMP Response Element-Binding Protein / Q000235:genetics; D006801:Humans; D007371:Interferon-gamma / Q000096:biosynthesis / Q000378:metabolism; D016753:Interleukin-10 / Q000276:immunology / Q000494:pharmacology; D007376:Interleukin-2 / Q000276:immunology; D015847:Interleukin-4 / Q000276:immunology / Q000494:pharmacology; D047908:Intracellular Signaling Peptides and Proteins / Q000276:immunology; D048031:JNK Mitogen-Activated Protein Kinases / Q000037:antagonists & inhibitors; D007694:Killer Cells, Natural / Q000187:drug effects / Q000276:immunology*; D008213:Lymphocyte Activation / Q000276:immunology; D048369:MAP Kinase Kinase 1 / Q000037:antagonists & inhibitors; D009369:Neoplasms / Q000276:immunology*; D010766:Phosphorylation / Q000187:drug effects; D011401:Promoter Regions, Genetic / Q000276:immunology; D011505:Protein-Tyrosine Kinases / Q000276:immunology; D020598:Proto-Oncogene Proteins c-myb / Q000235:genetics; D016271:Proto-Oncogene Proteins c-myc / Q000096:biosynthesis; D011944:Receptors, Androgen / Q000235:genetics; D015398:Signal Transduction / Q000187:drug effects / Q000276:immunology; D000072377:Syk Kinase; D018808:Transcription Factor AP-1 / Q000235:genetics; D016212:Transforming Growth Factor beta / Q000276:immunology* / Q000494:pharmacology*; D019139:Tumor Escape / Q000276:immunology*
chemical_list: C410798:AR protein, human; D000873:Anthracenes; C115163:CREB1 protein, human; D017362:Cyclic AMP Response Element-Binding Protein; C508609:IL10 protein, human; C508594:IL2 protein, human; C508598:IL4 protein, human; D007376:Interleukin-2; D047908:Intracellular Signaling Peptides and Proteins; C489427:MYC protein, human; D020598:Proto-Oncogene Proteins c-myb; D016271:Proto-Oncogene Proteins c-myc; D011944:Receptors, Androgen; D018808:Transcription Factor AP-1; D016212:Transforming Growth Factor beta; D016753:Interleukin-10; C432165:pyrazolanthrone; D015847:Interleukin-4; D007371:Interferon-gamma; D011505:Protein-Tyrosine Kinases; C000606896:SYK protein, human; D000072377:Syk Kinase; D048031:JNK Mitogen-Activated Protein Kinases; D048369:MAP Kinase Kinase 1; C482125:MAP2K1 protein, human
keywords: Immunosuppression; Interleukin-10 (IL-10); Interleukin-4 (IL-4); Natural killer (NK) cell; Signaling; Transcription regulation; Transforming growth factor beta (TGF-β)