Inhibition of blood vessel formation in tumors by IL-18-polarized M1 macrophages

Genes to Cells : Devoted to Molecular & Cellular Mechanisms
Yanjiang XingKenkichi Sugimoto

Abstract

We previously showed that interleukin (IL)-18 produced by NFSA cells induced the M1 type of macrophages in NFSA tumors, caused the destruction of endothelial cells in vitro and may have resulted in the necrosis of NFSA tumors by enhancing macrophage phagocytosis and cytotoxicity. However, the effect of IL-18 on blood vessel formation in vivo has not been elucidated. MS-K cells do not express il-18, and they form tumors with well-developed blood vessels. Here, we established IL-18-over-expressing MS-K cell clones (MS-K-IL-18) to address the roles of IL-18 in angiogenesis. The over-expression of IL-18 inhibited the proliferation rate of the MS-K-IL-18 cells in vitro and blood vessel formation in the MS-K-IL-18 tumors. Interestingly, CD14-positive cells from the MS-K-IL-18 tumor had up-regulated expression of the M1-type macrophage marker il-6 and down-regulated expression of interferon (ifn)-γ. Furthermore, FACS analysis showed more accumulation of CD11b+/CD80+ M1 macrophages in the MS-K-IL-18 tumors than in the parental MS-K tumor. Moreover, an in vitro coculture assay showed that MS-K-IL-18-conditioned medium (CM) stimulated macrophages to induce the apoptosis of endothelial cells. Cumulatively, our data showed that IL-18 inhib...Continue Reading

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Citations

May 14, 2016·Genes to Cells : Devoted to Molecular & Cellular Mechanisms·Yanjiang XingKenkichi Sugimoto
Oct 23, 2018·Genes to Cells : Devoted to Molecular & Cellular Mechanisms·Yijun TianKenkichi Sugimoto
Jul 12, 2019·Frontiers in Immunology·Erin Fahey, Sarah L Doyle

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