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

Dae Ho Cho, Hyunkeun Song, Yong Man Kim, Dong Houh, Dae Young Hur, Hyunjeong Park, Doyoung Yoon, Kwang Ho Pyun, Wang Jae Lee, Masashi Kurimoto, Yoon Berm Kim, Young Sang Kim, Inpyo Choi

Research output: Contribution to journalArticle

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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.

Original languageEnglish
Pages (from-to)2703-2709
Number of pages7
JournalCancer Research
Volume60
Issue number10
Publication statusPublished - 2000 May 15
Externally publishedYes

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Interleukin-18
Fas Ligand Protein
Melanoma
Oxygen
Natural Killer Cells
Interleukin-18 Receptors
Complementary DNA
Tumor Escape
Neoplasms
Antibodies
Immunoblotting
Reverse Transcription
Transfection

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

Cite this

Endogenous interleukin-18 modulates immune escape of murine melanoma cells by regulating the expression of Fas ligand and reactive oxygen intermediates. / Cho, Dae Ho; Song, Hyunkeun; Kim, Yong Man; Houh, Dong; Hur, Dae Young; Park, Hyunjeong; Yoon, Doyoung; Pyun, Kwang Ho; Lee, Wang Jae; Kurimoto, Masashi; Kim, Yoon Berm; Kim, Young Sang; Choi, Inpyo.

In: Cancer Research, Vol. 60, No. 10, 15.05.2000, p. 2703-2709.

Research output: Contribution to journalArticle

Cho, DH, Song, H, Kim, YM, Houh, D, Hur, DY, Park, H, Yoon, D, Pyun, KH, Lee, WJ, Kurimoto, M, Kim, YB, Kim, YS & Choi, I 2000, 'Endogenous interleukin-18 modulates immune escape of murine melanoma cells by regulating the expression of Fas ligand and reactive oxygen intermediates', Cancer Research, vol. 60, no. 10, pp. 2703-2709.
Cho, Dae Ho ; Song, Hyunkeun ; Kim, Yong Man ; Houh, Dong ; Hur, Dae Young ; Park, Hyunjeong ; Yoon, Doyoung ; Pyun, Kwang Ho ; Lee, Wang Jae ; Kurimoto, Masashi ; Kim, Yoon Berm ; Kim, Young Sang ; Choi, Inpyo. / Endogenous interleukin-18 modulates immune escape of murine melanoma cells by regulating the expression of Fas ligand and reactive oxygen intermediates. In: Cancer Research. 2000 ; Vol. 60, No. 10. pp. 2703-2709.
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AU - Hur, Dae Young

AU - Park, Hyunjeong

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AU - Pyun, Kwang Ho

AU - Lee, Wang Jae

AU - Kurimoto, Masashi

AU - Kim, Yoon Berm

AU - Kim, Young Sang

AU - Choi, Inpyo

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N2 - 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.

AB - 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.

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