Varney Michelle L, Olsen Kimberlee J, Mosley R Lee, Bucana Corazan D, Talmadge James E, Singh Rakesh K
Department of Pathology and Microbiology, 987660 Nebraska Medical Center, Omaha, NE 68198-7660, USA.
In Vivo. 2002 Nov-Dec;16(6):471-7.
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.
肿瘤相关巨噬细胞（TAM）已被证明在肿瘤血管生成中起重要作用。本研究的目的是确定由单核细胞趋化蛋白-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白细胞介素（IL）-8的表达。分离的人外周血单核细胞分泌低基础水平的IL-8。用M-CSF或MCP-1孵育单核细胞导致IL-8 mRNA和蛋白表达上调。MCP-1和M-CSF处理后单核细胞对IL-8的差异表达涉及NFkB转录因子的激活。用脂多糖（LPS）进一步激活导致单核细胞中IL-8分泌增加，但在单核细胞衍生的巨噬细胞（MDM）中未增加。MDM条件培养基在体外显著上调人恶性黑色素瘤细胞中IL-8的表达。总之，我们证明了对单核细胞募集、激活和分化至关重要的MCP-1和M-CSF差异调节IL-8表达，并可能在单核细胞/巨噬细胞介导的肿瘤血管生成中起重要作用。
