KMID : 0624620140470050286
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BMB Reports 2014 Volume.47 No. 5 p.286 ~ p.291
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Enhancement of phagocytosis and cytotoxicity in macrophages by tumor-derived IL-18 stimulation
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Xu Henan
Naoka Toyota Xing Yanjiang Yuuki Fujita Huang Zhijun Maki Touma Wu Qiong Kenkichi Sugimoto
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Abstract
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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.
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KEYWORD
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IL-18, macrophages, phagocytosis, Nos2, angiogenesis
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