IL-18 enhances ULBP2 expression through the MAPK pathway in leukemia cells |
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Authors: | Song Hyunkeun Kim Kyung-Eun Hur Daeyoung Lim Jong-Seok Yang Young Cho Byung Joo Kim Cherl-Hyun Kim Taesung Bang Saic Lee Wang Jae Park Hyunjeong Cho Daeho |
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Affiliation: | Department of Anatomy, Inje University College of Medicine, Pusan 614-735, Republic of Korea. |
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Abstract: | 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. |
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Keywords: | IL-18 Natural killer cells Tumor immunity ULBP NKG2D |
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