Abstract
NK cells are crucial components of the innate immune system, providing a first line of defense against infectious pathogens and tumors. IL-15 is the major physiologic growth factor responsible for NK cell differentiation, survival and cytolytic activity of mature NK cells. However, the exact regulatory mechanism of IL-15 on NK cell function is still unclear. In this study, we try to investigate the mechanism of IL-15 on NK cytolysis. Our results demonstrate that IL-15 treatment increased NKG2D transcripts and surface expression in NK cells. NKG2D or MICA blockade attenuated the up-regulation of IL-15 on NK cytolysis, demonstrating that the up-regulatory effect of IL-15 on NK cytolysis is at least partly dependent of the interaction of NKG2D and MICA. Furthermore, IL-15 augmented the expression of cytotoxic effector molecules (TRAIL and Perforin) and the phosphorylation of STAT1 and ERK1/2, which may also contribute the NK lysis. These results may have therapeutic implications when designing cytokine immunotherapy against cancer.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Animals
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Cell Line
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Coculture Techniques
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Cytotoxicity, Immunologic*
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Histocompatibility Antigens Class I / metabolism
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Humans
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Immunity, Innate
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Interferon-gamma / immunology
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Interleukin-15 / immunology*
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Killer Cells, Natural / cytology
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Killer Cells, Natural / immunology*
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Mitogen-Activated Protein Kinase 1 / genetics
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Mitogen-Activated Protein Kinase 1 / metabolism*
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Mitogen-Activated Protein Kinase 3 / genetics
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Mitogen-Activated Protein Kinase 3 / metabolism*
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NK Cell Lectin-Like Receptor Subfamily K
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Phosphorylation
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Receptors, Immunologic / genetics
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Receptors, Immunologic / metabolism*
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Receptors, Natural Killer Cell
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STAT1 Transcription Factor / genetics
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STAT1 Transcription Factor / metabolism*
Substances
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Histocompatibility Antigens Class I
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Interleukin-15
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KLRK1 protein, human
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MHC class I-related chain A
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NK Cell Lectin-Like Receptor Subfamily K
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Receptors, Immunologic
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Receptors, Natural Killer Cell
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STAT1 Transcription Factor
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STAT1 protein, human
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Interferon-gamma
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Mitogen-Activated Protein Kinase 1
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Mitogen-Activated Protein Kinase 3