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KMID : 0624620140470050286
BMB Reports
2014 Volume.47 No. 5 p.286 ~ p.291
Enhancement of phagocytosis and cytotoxicity in macrophages by tumor-derived IL-18 stimulation
Xu Henan

Naoka Toyota
Xing Yanjiang
Yuuki Fujita
Huang Zhijun
Maki Touma
Wu Qiong
Kenkichi Sugimoto
Abstract
Inoculation of mice with the murine NFSA cell line caused the formation of large tumors with necrotic tumor cores. FACS analysis revealed accumulations of CD11b+ cells in the tumors. Microarray analysis indicated that the NFSA cells expressed a high level of the pro-inflammatory factor interleukin-18 (il-18), which is known to play a critical role in macrophages. However, little is known about the physiological function of IL-18-stimulated macrophages. Here, we provide direct evidence that IL-18 enhances the phagocytosis of RAW264 cells and peritoneal macrophages, accompanied by the increased expression of tumor necrosis factor (tnf-¥á), interleukin-6 (il-6) and inducible nitric oxide synthase (Nos2). IL-18-stimulated RAW264 cells showed an enhanced cytotoxicity to endothelial F-2 cells via direct cell-to-cell interaction and the secretion of soluble mediators. Taken together, our results demonstrate that tumor-derived IL-18 plays an important role in the phagocytosis of macrophages and that IL-18-stimulated macrophages may damage tumor endothelial cells.
KEYWORD
IL-18, macrophages, phagocytosis, Nos2, angiogenesis
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