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.
Jung
Min Kyung
MK
Department of Life Science, Sookmyung Women's University, Chungpa-Dong 2-Ka, Yongsan-ku, Seoul 140-742, Republic of Korea.
Song
Hyun Keun
HK
Kim
Kyung-Eun
KE
Hur
Dae Young
DY
Kim
Taesung
T
Bang
Saic
S
Park
Hyunjeong
H
Cho
Dae Ho
DH
D000111:Acetylcysteine / Q000494:pharmacology; D000818:Animals; D002465:Cell Movement / Q000187:drug effects; D005419:Flavonoids / Q000494:pharmacology; D016166:Free Radical Scavengers / Q000494:pharmacology; D020382:Interleukin-18 / Q000235:genetics / Q000494:pharmacology / Q000502:physiology*; D008546:Melanoma, Experimental / Q000276:immunology / Q000473:pathology*; D051379:Mice; D019950:Mitogen-Activated Protein Kinase 1 / Q000037:antagonists & inhibitors / Q000378:metabolism; D048052:Mitogen-Activated Protein Kinase 3 / Q000037:antagonists & inhibitors / Q000378:metabolism; D020928:Mitogen-Activated Protein Kinases / Q000037:antagonists & inhibitors / Q000378:metabolism*; D010766:Phosphorylation; D047428:Protein Kinase Inhibitors / Q000494:pharmacology; D017382:Reactive Oxygen Species / Q000032:analysis / Q000037:antagonists & inhibitors / Q000378:metabolism*; D014162:Transfection
D005419:Flavonoids; D016166:Free Radical Scavengers; D020382:Interleukin-18; D047428:Protein Kinase Inhibitors; D017382:Reactive Oxygen Species; D019950:Mitogen-Activated Protein Kinase 1; D048052:Mitogen-Activated Protein Kinase 3; D020928:Mitogen-Activated Protein Kinases; C093973:2-(2-amino-3-methoxyphenyl)-4H-1-benzopyran-4-one; D000111:Acetylcysteine