IL-18 enhances the migration ability of murine melanoma cells through the generation of ROI and the MAPK pathway

Interleukin-18 (IL-18) has multiple effects on various cells that are involved in immune escape of murine melanoma cells and in the inflammatory responses. This study investigated the effect of IL-18 on the ability of murine melanoma cells to migrate by using B16F10 cells and the IL-18 antisense transfectants of B16F10 cells (the B16F10/IL-18 antisense transfectant). The B16F10 cells were more able to migrate than were the B16F10/IL-18 antisense transfectants. An exogenous IL-18 treatment improved the ability of the B16F10/IL-18 antisense transfectant cells to migrate, indicating that IL-18 enhanced the migration ability of melanoma cells. To determine the signaling mechanisms involved in IL-18-enhanced migration, we measured the ROI levels. It was found that the ROI levels were increased by IL-18, and an antioxidant, N-acetyl-l-cystein (NAC), blocked the effect of IL-18 on migration, suggesting the involvement of ROI in the signal transduction of IL-18-enhanced cell migration. IL-18-enhanced cell migration was also reduced by PD98059. In addition, the level of ERK1/2 phosphorylation was markedly increased by treating with exogenous IL-18 at 20 min. These results suggest that IL-18 enhances the ability of melanoma cells to migrate via the generation of ROI and the MAPK pathway.