title: Enhancement of phagocytosis and cytotoxicity in macrophages by tumor-derived IL-18 stimulation.
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-α), 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.
authors.affiliation: Department of Cell Science, Faculty of Graduate School of Science and Technology, Niigata University, Nishi-ku, Niigata 950-2181, Japan.
authors.forename: Xu
authors.initials: X
authors.lastname: Henan
authors.affiliation: Department of Cell Science, Faculty of Graduate School of Science and Technology, Niigata University, Nishi-ku, Niigata 950-2181, Japan.
authors.forename: Naoka
authors.initials: N
authors.lastname: Toyota
authors.affiliation: Department of Cell Science, Faculty of Graduate School of Science and Technology, Niigata University, Nishi-ku, Niigata 950-2181, Japan.
authors.forename: Xing
authors.initials: X
authors.lastname: Yanjiang
authors.affiliation: Department of Cell Science, Faculty of Graduate School of Science and Technology, Niigata University, Nishi-ku, Niigata 950-2181, Japan.
authors.forename: Yuuki
authors.initials: Y
authors.lastname: Fujita
authors.affiliation: School of Life Science and Technology, State Key Laboratory of Urban Water Resource and Environment, Harbin Institute of Technology, Harbin, 150001, China.
authors.forename: Huang
authors.initials: H
authors.lastname: Zhijun
authors.affiliation: Department of Cell Science, Faculty of Graduate School of Science and Technology, Niigata University, Nishi-ku, Niigata 950-2181, Japan.
authors.forename: Maki
authors.initials: M
authors.lastname: Touma
authors.affiliation: School of Life Science and Technology, State Key Laboratory of Urban Water Resource and Environment, Harbin Institute of Technology, Harbin, 150001, China.
authors.forename: Wu
authors.initials: W
authors.lastname: Qiong
authors.affiliation: Department of Cell Science, Faculty of Graduate School of Science and Technology, Niigata University, Nishi-ku, Niigata 950-2181, Japan.
authors.forename: Kenkichi
authors.initials: K
authors.lastname: Sugimoto
mesh_terms: D000818:Animals; D039481:CD11b Antigen / Q000378:metabolism; D002460:Cell Line; D045744:Cell Line, Tumor; D003602:Cytotoxicity, Immunologic; D042783:Endothelial Cells / Q000276:immunology; D015870:Gene Expression; D020382:Interleukin-18 / Q000276:immunology*; D015850:Interleukin-6 / Q000235:genetics; D008262:Macrophage Activation; D008264:Macrophages / Q000276:immunology*; D017737:Macrophages, Peritoneal / Q000276:immunology; D051379:Mice; D008809:Mice, Inbred C3H; D009374:Neoplasms, Experimental / Q000098:blood supply / Q000235:genetics / Q000276:immunology*; D052247:Nitric Oxide Synthase Type II / Q000235:genetics; D010587:Phagocytosis; D011994:Recombinant Proteins / Q000276:immunology; D014409:Tumor Necrosis Factor-alpha / Q000235:genetics
chemical_list: D039481:CD11b Antigen; D020382:Interleukin-18; D015850:Interleukin-6; D011994:Recombinant Proteins; D014409:Tumor Necrosis Factor-alpha; D052247:Nitric Oxide Synthase Type II; C496317:Nos2 protein, mouse