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Title 

Endogenous interleukin-18 modulates immune escape of murine melanoma cells by regulating the expression of fas ligand and reactive oxygen intermediates

Authors 

Dae Ho ChoHyun Keun SongYong Man KimDong HoughDae Young HurHyun Jeong ParkDo Young YoonKwang Ho PyunWang Jae LeeMasashi KurimotoYoon Berm KimYoung Sang KimIn Pyo Choi

Publisher 

American Association for Cancer Research

Issue Date 

2000

Citation 

Cancer Research, vol. 60, no. 10, pp. 2703-2709

Keywords 

FAS ligandinterleukin 18interleukin 18 receptorligandreactive oxygen metaboliteanimal cellcell survivalmelanomamelanoma cellnatural killer cell mediated cytotoxicity

Abstract 

It has been known that melanoma cells can suppress the immune system by the Fas ligand. The present study investigated whether interleukin (IL)-18, which can enhance Fas ligand expression, is produced by B16F10 melanoma cells and is involved in immune escape of tumor cells. Immunohistology, reverse transcription-PCR, intracellular fluorescence-activated cell-sorting analysis, and immunoblotting demonstrated that melanoma cells express IL-18. C57BL/6 splenocytes cultured with culture supernatants of B16F10 melanoma cells enhanced IFN-χ production, which was blocked by anti-IL-18 antibody, indicating that IL-18 in the culture supernatants is functional. In addition to IL-18, the IL-18 receptor was also detected in B16F10 melanoma cells, suggesting a role of this cytokine in regulating the functions of B16F10 melanoma cells. The functional effect of IL-18 on B16F10 melanoma cells was shown by reduction of Fas ligand expression in cells treated with anti-IL-18 antibody or transfected with IL-18 antisense cDNA. In addition, the same treatments decreased intracellular reactive oxygen intermediate levels in B16F10 melanoma cells, indicating that IL-18 regulates reactive oxygen intermediate production, which is involved in Fas ligand expression. Furthermore, transfection of IL-18 antisense cDNA into melanoma cells increased the susceptibility of tumor cells to natural killer cells in vitro. When IL-18 antisense transfectants were implanted into syngeneic mice, severe reduction of tumor cell growth was observed with concomitant infiltrated natural killer cells in the tumor area. Taken together, these results demonstrate that IL-18 has a critical role as a survival factor for B16F10 melanoma cells.

ISSN 

0008-5472

Appears in Collections

1. Journal Articles > Journal Articles

Registered Date

2017-04-19


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