ORIGINAL ARTICLESVitamin C downregulates interleukin-18 production by increasing reactive oxygen intermediate and mitogen-activated protein kinase signalling in B16F10 murine melanoma cellsCho, Daehoa; Hahm, Eunsilb; Kang, Jae Seungb; Kim, Young-Inb; Yang, Yoolheea; Park, Jong Hoona; Kim, Daejinb; Kim, Seonghanb; Kim, Yeong Seokc; Hur, Daeyoungc; Park, Hyunjeongd; Pang, Saice; Il Hwang, Youngb; Lee, Wang JaebAuthor Information aDepartment of Life Science, Sookmyung Women's University, Seoul, Korea, bDepartment of Anatomy and Tumor Immunity Medical Research Center, Seoul National University College of Medicine, Seoul, Korea, cDepartment of Anatomy, Inje University College of Medicine, Seoul, Korea, dDepartment of Dermatology, St Mary's Hospital, The Catholic University of Korea, Seoul, Korea, and eDepartment of Plastic Surgery, College of Medicine, Sung Kyun Kwan University, Seoul, Korea. Sponsorship: This study was supported by a grant from the International Mobile Telecommunications 2000 R&D Project, Ministry of Information and Communication, Republic of Korea (01-PJ11-PG9-01BT00A-0020). Correspondence and requests for reprints to Wang Jae Lee, Department of Anatomy, Seoul National University College of Medicine, 28 Yongon-dong Chongno-gu, Seoul, 110-799 Korea. Tel: +82 2 740 8208; fax: +82 2 745 9528; e-mail: [email protected] Received 23 January 2003 Accepted 30 June 2003 Melanoma Research: December 2003 - Volume 13 - Issue 6 - p 549-554 Buy 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 up-regulating 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. © 2003 Lippincott Williams & Wilkins, Inc.