Vitamin C downregulates interleukin-18 production by increasing reactive oxygen intermediate and mitogen-activated protein kinase signalling in B16F10 murine melanoma cells

Daeho Cho, Eunsil Hahm, Jae Seung Kang, Young In Kim, Yoolhee Yang, Jong Hoon Park, Daejin Kim, Seonghan Kim, Yeong Seok Kim, Daeyoung Hur, Hyunjeong Park, Saic Pang, Young Hwang, Wang Jae Lee

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11 Citations (Scopus)

Abstract

We recently reported that interleukin-18 (IL-18) is highly expressed in malignant skin tumours such as melanomas, and may play a key role in the malignancy of such tumours. This study was designed to investigate the mechanisms of IL-18 regulation by vitamin C in B16F10 murine melanoma cells. Cells were treated with vitamin C, and the expression of IL-18 was measured by reverse transcription-polymerase chain reaction and intracellular flow cytometry analysis. Decreased IL-18 production and a significant reduction in IL-18 mRNA transcript were detected in cells treated with vitamin C. The effect of vitamin C treatment was blocked by the antioxidant N-acetyl-L-cysteine, suggesting that vitamin C affects IL-18 expression by upregulating intracellular reactive oxygen Intermediate (ROI) levels. To investigate whether the mitogen-activated protein kinase (MAPK) signalling pathway is involved in the downregulation of IL-18 production, cells were pretreated with SB203580, an inhibitor of p38 MAPK, prior to the addition of vitamin C. This pretreatment blocked the decrease in IL-18 production. However, vitamin C treatment enhanced the expression of phosphorylated p38 MAPK. Taken together, we conclude that vitamin C increases intracellular ROI levels, and regulates IL-18 production through the MAPK signalling pathway.

Original languageEnglish
Pages (from-to)549-554
Number of pages6
JournalMelanoma Research
Volume13
Issue number6
DOIs
Publication statusPublished - 2003 Dec 1

Keywords

  • Interleukin-18
  • Melanoma
  • Mitogen-activated protein kinase
  • Reactive oxygen intermediates
  • Vitamin C
  • p38

ASJC Scopus subject areas

  • Oncology
  • Dermatology
  • Cancer Research

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    Cho, D., Hahm, E., Kang, J. S., Kim, Y. I., Yang, Y., Park, J. H., Kim, D., Kim, S., Kim, Y. S., Hur, D., Park, H., Pang, S., Hwang, Y., & Lee, W. J. (2003). Vitamin C downregulates interleukin-18 production by increasing reactive oxygen intermediate and mitogen-activated protein kinase signalling in B16F10 murine melanoma cells. Melanoma Research, 13(6), 549-554. https://doi.org/10.1097/00008390-200312000-00002