Journal
CELLULAR IMMUNOLOGY
Volume 290, Issue 1, Pages 52-61Publisher
ACADEMIC PRESS INC ELSEVIER SCIENCE
DOI: 10.1016/j.cellimm.2014.05.001
Keywords
Natural killer (NK) cell; Immunosuppression; Transforming growth factor beta (TGF-beta); Interleukin-10 (IL-10); Interleukin-4 (IL-4); Signaling; Transcription regulation
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Funding
- National Research Foundation (NRF) - Korean government (MSIP) [2011-0030086]
- National Research Foundation of Korea [2011-0030086] Funding Source: Korea Institute of Science & Technology Information (KISTI), National Science & Technology Information Service (NTIS)
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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.
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