IL-2/IL-18 prevent the down-modulation of NKG2D by TGF-β in NK cells via the c-Jun N-terminal kinase (JNK) pathway

Hyunkeun Song, Dae Young Hur, Kyung Eun Kim, Hyunjeong Park, Taesung Kim, Chul woo Kim, Saic Bang, Dae Ho Cho

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42 Citations (Scopus)


TGF-β is known to play a major role for the reduced NKG2D expression seen in cancer patients. However, the mechanisms for reduced TGF-β-induced down-regulation of NKG2D are unclear. In this study, we observed that IL-2/IL-18 increased the NKG2D expression in the TGF-β treated NK cell line in a dose-dependent manner. Incubation with the JNK inhibitor SP600125 inhibited the NKG2D expression induced by IL-2/IL-18 in the TGF-β treated human NK cell line. Moreover, the NK cytotoxicity assay showed that the reduced NK cytotoxicity by TGF-β was recovered by IL-2/IL-18 treatment. The results indicate that IL-2/IL-18 strongly prevented the TGF-β-induced NKG2D down-regulation in NK cells via the JNK pathway. Taken together, the protected expression of NKG2D by IL-2/IL-18 provides insight into the mechanism of NKG2D regulation and it also supplied useful information for creating a novel therapeutic approach to treat TGF-β-secreting cancer cells.

Original languageEnglish
Pages (from-to)39-45
Number of pages7
JournalCellular Immunology
Issue number1
Publication statusPublished - 2006 Jul

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.


  • IL-18
  • IL-2
  • NK cells
  • NKG2D
  • TGF-β

ASJC Scopus subject areas

  • Immunology


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