Journal
IMMUNOLOGY LETTERS
Volume 120, Issue 1-2, Pages 103-107Publisher
ELSEVIER SCIENCE BV
DOI: 10.1016/j.imlet.2008.07.007
Keywords
IL-18; Natural killer cells; Tumor immunity; ULBP; NKG2D
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Funding
- Korea Science & Engineering Foundation (KOSEF)
- Research Center for Women's Disease [R11-2005-017-02003-0]
- Seoul Research and Business Development Program [10582]
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Expression of UL16-binding proteins (ULBPs) has been reported in various cancers, such as leukemia and melanoma, and also in some other cancer cell lines. However, the factors that modulate the expression of ULBPs are not well defined. In this study, we investigated the effects of IL-18 on the expression of NKG2D ligands in leukemia cells. IL-18 treatment increased ULBP2 expression in leukemia cells at the mRNA and protein levels. In addition, PD98059 (an ERK1/2 MAPK inhibitor) and SP600125 (a JNK inhibitor) attenuated IL-18-induced ULBP2 expression in a dose-dependent manner. We observed that ERK1/2 and JNK MAPK phosphorylation increased upon treatment with IL-18. IL-18 elevated CD107a expression in cancer cells and increased the cytotoxic activity of NK cells; therefore, we propose that IL-18 increases the susceptibility of target cells by inducing surface expression of ULBP2. Taken together, these findings suggest that IL-18 may play a critical role in regulating ULBP2 expression via the ERK1/2 and JNK MAPK pathways in leukemia cells. (C) 2008 Elsevier B.V. All rights reserved.
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