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 language | English |
---|---|
Pages (from-to) | 549-554 |
Number of pages | 6 |
Journal | Melanoma Research |
Volume | 13 |
Issue number | 6 |
DOIs | |
Publication status | Published - 2003 Dec |
Externally published | Yes |
Keywords
- Interleukin-18
- Melanoma
- Mitogen-activated protein kinase
- Reactive oxygen intermediates
- Vitamin C
- p38
ASJC Scopus subject areas
- Oncology
- Dermatology
- Cancer Research