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首页> 外文期刊>Cell biology international. >Bystander effect of normal fibroblasts for macrophages co-cultured with susceptible transformed target cells.
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Bystander effect of normal fibroblasts for macrophages co-cultured with susceptible transformed target cells.

机译:正常成纤维细胞对巨噬细胞与易感转化靶细胞共培养的旁观者效应。

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摘要

Macrophages attack and kill pathologically changed, transformed and tumor cells. However, in some cases they may also support tumor growth, modulate the action of anticancer drugs, and even facilitate the development of drug resistance in tumor cells. Here we present data that bystander fibroblasts NIH3T3 were not only resistant to murine macrophages J774.2 but also blocked their killing action towards murine transformed fibroblasts L929. Macrophages were isolated from mixed cultures by means of CD11b specific immunomagnetic beads, and changes induced by their former co-culturing were studied using DNA microarray technology and other tests. An expression of candidate genes coding for cytokines and for signal transduction pathway proteins was estimated in macrophages in different variants of their co-culture with target cells. Changes in expression of mRNA for interleukin 1beta, NFkappaB, IkappaBalpha, gadd45, and CD5 were detected as the most prominent in the macrophages co-cultured with the transformed cells. Bystander NIH3T3 fibroblasts abolished these changes in the macrophages J774.2, and the level of expression of the above mentioned genes was close to the level seen in the macrophages which did not exert cytotoxicity towards the target fibroblasts. Potential implications and research perspectives of using the macrophage-target cell co-cultures with different bystander cellular partners are discussed.
机译:巨噬细胞攻击并杀死病理改变,转化的肿瘤细胞。但是,在某些情况下,它们也可能支持肿瘤生长,调节抗癌药的作用,甚至促进肿瘤细胞中耐药性的发展。在这里,我们提供的数据表明,旁观者成纤维细胞NIH3T3不仅对鼠巨噬细胞J774.2具有抗性,而且还阻断了它们对鼠类转化成纤维细胞L929的杀伤作用。通过CD11b特异性免疫磁珠从混合培养物中分离出巨噬细胞,并使用DNA微阵列技术和其他测试研究了它们先前共培养引起的变化。在巨噬细胞中与靶细胞共培养的不同变体中,估计了编码细胞因子和信号转导途径蛋白的候选基因的表达。在与转化细胞共培养的巨噬细胞中,白介素1β,NFkappaB,IkappaBalpha,gadd45和CD5的mRNA表达变化被检测为最明显。旁观者NIH3T3成纤维细胞消除了巨噬细胞J774.2中的这些变化,并且上述基因的表达水平接近于巨噬细胞中看到的水平,其对靶成纤维细胞没有细胞毒性。讨论了与不同旁观者细胞伴侣一起使用巨噬细胞-靶细胞共培养物的潜在影响和研究前景。

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