A novel co-culture model for investigation of the effects of LPS-induced macrophage-derived cytokines on brain endothelial cells.
A novel co-culture model for investigation of the effects of LPS-induced macrophage-derived cytokines on brain endothelial cells.
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DOI：
10.1371/journal.pone.0288497
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发表时间：
2023
期刊：
影响因子：
3.7
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中科院分区：
文献类型：
--
作者：
为了研究与全身炎症相关的巨噬细胞源性炎症介质对脑内皮细胞的影响，我们建立了由bEnd.3细胞和LPS激活的Raw 264.7细胞组成的共培养系统，并进行了其细胞因子分析。将共培养模型的细胞因子谱与腹膜内注射 LPS 治疗的小鼠的细胞因子谱进行比较。我们发现，在分析的细胞因子中，有八种细胞因子/趋化因子在体内小鼠和体外共培养模型中类似地上调。与共培养模型相反，仅由 LPS 激活的 bEnd.3 细胞组成的常见单一培养系统的细胞因子谱与体内小鼠模型的细胞因子谱几乎没有相似之处。这些结果表明，bEnd.3细胞与LPS激活的Raw 264.7细胞的共培养是比LPS激活的bEnd.3细胞的普通单一培养更好的模型，可用于研究内皮细胞中全身炎症诱导神经炎症的分子机制。此外，纤维蛋白原对共培养物中的 bEnd.3 细胞以及经 LPS 处理的阿尔茨海默病动物模型中脑血管的粘附均有所增加。据我们所知，这是第一个利用 bEnd.3 细胞与 LPS 激活的 Raw 264.7 细胞共培养作为体外模型来研究巨噬细胞衍生的炎症介质对脑内皮细胞的影响。
In order to study effects of macrophage-derived inflammatory mediators associated with systemic inflammation on brain endothelial cells, we have established a co-culture system consisting of bEnd.3 cells and LPS-activated Raw 264.7 cells and performed its cytokine profiling. The cytokine profile of the co-culture model was compared to that of mice treated with intraperitoneal LPS injection. We found that, among cytokines profiled, eight cytokines/chemokines were similarly upregulated in both in vivo mouse and in vitro co-culture model. In contrast to the co-culture model, the cytokine profile of a common mono-culture system consisting of only LPS-activated bEnd.3 cells had little similarity to that of the in vivo mouse model. These results indicate that the co-culture of bEnd.3 cells with LPS-activated Raw 264.7 cells is a better model than the common mono-culture of LPS-activated bEnd.3 cells to investigate the molecular mechanism in endothelial cells, by which systemic inflammation induces neuroinflammation. Moreover, fibrinogen adherence both to bEnd.3 cells in the co-culture and to brain blood vessels in a LPS-treated animal model of Alzheimer’s disease increased. To the best of our knowledge, this is the first to utilize bEnd.3 cells co-cultured with LPS-activated Raw 264.7 cells as an in vitro model to investigate the consequence of macrophage-derived inflammatory mediators on brain endothelial cells.
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影响因子：
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