Monocyte/macrophage recruitment, activation and differentiation modulate interleukin-8 production: a paracrine role of tumor-associated macrophages in tumor angiogenesis.
Monocyte/macrophage recruitment, activation and differentiation modulate interleukin-8 production: a paracrine role of tumor-associated macrophages in tumor angiogenesis.
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发表时间：
2002-11
期刊：
影响因子：
2.3
通讯作者：
M. Varney;Kimberlee J Olsen;R. Mosley;C. Bucana;J. Talmadge;Rakesh K. Singh
中科院分区：
文献类型：
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作者：
M. Varney;Kimberlee J Olsen;R. Mosley;C. Bucana;J. Talmadge;Rakesh K. Singh
肿瘤相关巨噬细胞()在肿瘤血管生成中发挥重要作用。本研究旨在探讨单核细胞趋化蛋白-1(MCP-1)和巨噬细胞集落刺激因子(M-CSF)介导的单核细胞募集、激活和分化是否调节血管生成因子IL-8的表达。分离的人外周血单核细胞分泌基础水平较低的IL-8。单核细胞与M-CSF或MCP-1孵育后，IL-8mRNA和蛋白表达上调。单核细胞在MCP-1和M-CSF处理后IL-8的差异表达涉及NFkB转录因子的激活。进一步用脂多糖(LPS)激活可增加单核细胞分泌IL-8，但对单核细胞来源的巨噬细胞(MDM)无影响。MDM条件培养液可显著上调人恶性黑色素瘤细胞IL-8的表达。综上所述，我们证明了单核细胞募集、激活和分化的关键分子MCP-1和M-CSF对IL-8的表达起着不同的调节作用，并可能在单核/巨噬细胞介导的肿瘤血管生成中发挥重要作用。
Tumor-associated macrophages (TAM) have been shown to play an important role in tumor angiogenesis. The purpose of this study was to determine whether monocyte recruitment, activation and differentiation mediated by monocyte chemotactic protein-1 (MCP-1) and macrophage colony stimulating factor (M-CSF) modulate the expression of the angiogenic factor, Interleukin (IL)-8. Isolated human peripheral blood monocytes secreted low basal levels of IL-8. Incubation of monocytes with M-CSF or MCP-1 resulted in an up-regulation of IL-8 mRNA and protein expression. The differential expression of IL-8 by monocytes following MCP-1 and M-CSF treatments involved activation of the NFkB transcription factor. Further activation with lipopolysaccharide (LPS) caused an increase in IL-8 secretion in monocytes but not in monocyte-derived macrophages (MDM). MDM-conditioned media significantly up-regulated IL-8 expression in human malignant melanoma cells in vitro. In summary, we demonstrated that MCP-1 and M-CSF, critical for monocyte recruitment, activation and differentiation, differentially regulate IL-8 expression and may play an important role in monocyte/macrophage-mediated tumor angiogenesis.