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主题：联合应用肿瘤相关巨噬细胞的GM-CSF处理和M-CSF抑制，体外诱导树突状细胞的信号+ h9 F" _- O( F1 K' W
1 M; p# a6 H; x- D7 x. h3 T0 S9 b8 i3 N说明：原文来源自Int J Oncol. 2011 Mar 3，由干细胞之家新闻小组成员deron翻译（转帖请注明）。8 u; R, E( K' }6 y: g0 a# l# g) m
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翻译内容：9 q2 |" H2 p0 y3 a" W
巨噬细胞具可塑性，肿瘤相关巨噬细胞（TAM）可以在肿瘤微环境中发挥免疫抑制的功能。因而，在本研究中，我们致力于在体外通过改变细胞因子信号来调整TAM。尽管TAM为球型且对培养皿呈现较低黏附性，但是粒性巨噬细胞集落刺激因子（GM-CSF）对TAM的单独处理不能够引起M1（包括IL-1β、TNFα和CXCL-10）或者M2（包括CD36、CD206和CCL17）分子的表达变化。当巨噬细胞集落刺激因子（M-CSF）信号被抗M-CSF受体（M-CSFR）的siRNA抑制、同时联合用GM-CSF处理时，TAM的信号转导途径发生改变，并且树突状细胞标志性的STAT1、STAT5和STAT6表达上调。然而，相同的处理没有改变TAM的M1/M2标记分子的表达模式。关于NF-κB途径， GM-CSF和M-CSFR siRNA的联合处理能够显著诱导p65的表达——后者通常不在TAM中表达，同时TAM的p50和p105表达未受实验处理的影响。研究结果提示：基于M1/M2标记表达分析，本研究的实验模型不能诱导TAM向单核细胞来源的树突状细胞样表型分化，但是该实验模型能够修改细胞信号途径趋向于树突状细胞的模式。因此，现有数据表明TAM具有向树突状细胞样信号转导模式转化的可塑性，并且肿瘤微环境的改变可潜在地逆转TAM的免疫抑制特性。0 j/ ^& ?4 e, u" w1 N" I; a
9 _ E8 H# `4 g- r% e/ h原摘要：Macrophages demonstrate plasticity, and tumor-associated macrophages (TAM) can function as immunosuppressive cells in the tumor microenvironment. Therefore, in this study, we aimed to reprogram TAM in vitro with cytokine signal alteration. Granulocyte macrophage colony stimulating factor (GM-CSF) treatment alone did not lead to changes in the expression of M1 (including IL-1β, TNFα and CXCL-10) or M2 (including CD36, CD206 and CCL17) molecules by TAM in vitro, although they adopted a round morphology and were less adhesive to the culture dish. When macrophage colony stimulating factor (M-CSF) signals were suppressed by siRNA against the M-CSF receptor (M-CSFR) in conjunction with GM-CSF treatment, the signal transduction pathway of TAM was altered, and the expression of STAT1, STAT5 and STAT6, which are usually expressed by dendritic cells, was increased. However, the same treatment did not alter the TAM expression pattern of M1/M2 marker molecules. With respect to the NF-κB pathway, GM-CSF and M-CSFR siRNA combination treatment significantly induced the expression of p65, which is usually not expressed by TAM, while p50 and p105 expression by TAM was not affected by the treatment. These findings indicate that our model could not redirect TAM to a monocyte-derived dendritic cell-like phenotype based on the analysis of M1/M2 marker expression, but it was able to modify cell signaling pathways toward a dendritic cell-like pattern. Therefore, the present data suggest that TAM demonstrate plasticity toward dendritic cell-like signal transduction patterns, and that the alteration of the tumor microenvironment has the potential to reverse the immunosuppressive properties of TAM.# N9 [2 p: ?& z+ g
. X V, y$ }2 J$ j* v原文：http://www.ncbi.nlm.nih.gov/pubmed/21373754: g3 W' `/ l3 j$ K# w% i/ b
5 K( X, S2 o$ G/ A9 M$ c& [说明：文章简单来讲就是想把巨噬细胞往树突状细胞方向诱导，加了几种因子后发现虽然从表型上来讲诱导没成功，但是诱导组的信号转导途径已经开始向树突状细胞靠近了~感觉有点糊弄人那… |
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发表于 2011-3-7 20:37
