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  • Title: IL-2/IL-18 prevent the down-modulation of NKG2D by TGF-beta in NK cells via the c-Jun N-terminal kinase (JNK) pathway.
    Author: Song H, Hur DY, Kim KE, Park H, Kim T, Kim CW, Bang S, Cho DH.
    Journal: Cell Immunol; 2006 Jul; 242(1):39-45. PubMed ID: 17070508.
    Abstract:
    TGF-beta is known to play a major role for the reduced NKG2D expression seen in cancer patients. However, the mechanisms for reduced TGF-beta-induced down-regulation of NKG2D are unclear. In this study, we observed that IL-2/IL-18 increased the NKG2D expression in the TGF-beta 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-beta treated human NK cell line. Moreover, the NK cytotoxicity assay showed that the reduced NK cytotoxicity by TGF-beta was recovered by IL-2/IL-18 treatment. The results indicate that IL-2/IL-18 strongly prevented the TGF-beta-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-beta-secreting cancer cells.
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