IL-18 enhances ULBP2 expression through the MAPK pathway in leukemia cells

Hyunkeun Song, Kyung Eun Kim, Daeyoung Hur, Jong Seok Lim, Young Yang, Byung Joo Cho, Cherl hyun Kim, Taesung Kim, Saic Bang, Wang Jae Lee, Hyunjeong Park, Dae Ho Cho

Research output: Contribution to journalArticlepeer-review

11 Citations (Scopus)

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.

Original languageEnglish
Pages (from-to)103-107
Number of pages5
JournalImmunology Letters
Volume120
Issue number1-2
DOIs
Publication statusPublished - 2008 Sept 30

Bibliographical note

Funding Information:
This study was supported by the Korea Science & Engineering Foundation (KOSEF) through the Tumor Immunity Medical Research Center (TIMRC) at Seoul National University College of Medicine and through the Research Center for Women's Disease (RCWD; SRC program (R11-2005-017-02003-0)) at Sookmyung Women's University and by Seoul Research and Business Development Program (Seoul R&BD Program (10582)).

Keywords

  • IL-18
  • NKG2D
  • Natural killer cells
  • Tumor immunity
  • ULBP

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

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