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

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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
Author(s)
Dae Ho Cho; Hyun Keun Song; Yong Man Kim; Dong Hough; Dae Young Hur; Hyun Jeong Park; Do Young Yoon; Kwang Ho Pyun; Wang Jae Lee; Masashi Kurimoto; Yoon Berm Kim; Young Sang Kim; In Pyo Choi
Bibliographic Citation
Cancer Research, vol. 60, no. 10, pp. 2703-2709
Publication Year
2000
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
Publisher
Amer Assoc Cancer Research
Type
Article
Appears in Collections:
Division of Biomedical Research > Immunotherapy Research Center > 1. Journal Articles
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