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首页> 外文期刊>Cell Communication and Signaling >Activation of C6 glioblastoma cell ceruloplasmin expression by neighboring human brain endothelia-derived interleukins in an in vitro blood–brain barrier model system
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Activation of C6 glioblastoma cell ceruloplasmin expression by neighboring human brain endothelia-derived interleukins in an in vitro blood–brain barrier model system

机译：在体外血脑屏障模型系统中，邻近人脑内皮源白介素激活C6胶质母细胞瘤细胞铜蓝蛋白表达

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Background Iron transport across the blood–brain barrier (BBB) involves the cooperation of brain microvascular endothelial cells (BMVEC) and their neighboring astrocytes. Astrocytes secrete a soluble form of ceruloplasmin (sCp) which, in turn, acts to export iron from ferroportin (Fpn) on the basolateral surface of BMVEC. Although regulation of astrocyte sCp gene expression has been demonstrated to be influenced by interleukin-1 beta (IL-1β) and interleukin-6 (IL-6), the role of neighboring BMVEC in this regulation has yet to be determined and is the basis for this work. Results We provide evidence that human BMVEC (hBMVEC) IL-1β and IL-6 positively influence the expression of sCp transcript by neighboring C6 glioma cells (astrocytes). The effect of hBMVEC on C6 glioma sCp expression at the level of transcript and protein was repressed via the addition of IL-1β and IL-6 pathway inhibitors (IL-1 receptor antagonist protein and SC144, respectively). Stimulation of hBMVEC interleukin gene expression by apical exposure to bacterial endotoxin lipopolysaccharide significantly enhanced hBMVEC-mediated C6 glioma sCp gene expression. Conclusion hBMVEC influence the gene expression of neighboring C6 glioma sCp. This change in gene expression is mediated by the secretion of IL-1β and IL-6 from hBMVEC. Furthermore, the hBMVEC-induced increase in neighboring C6 glioma sCp gene expression leads to an increased rate of hBMVEC iron efflux. Taken together, our results indicate that hBMVEC-secreted cytokine activity increases the gene expression of neighboring C6 glioma sCp, which reciprocally acts on basolateral hBMVEC Fpn to enhance brain iron import.
机译：背景技术跨血脑屏障（BBB）的铁运输涉及脑微血管内皮细胞（BMVEC）及其邻近星形胶质细胞的合作。星形胶质细胞分泌可溶性形式的铜蓝蛋白（sCp），进而从BMVEC基底外侧表面的铁转运蛋白（Fpn）中输出铁。尽管已证明星形胶质细胞sCp基因表达的调节受白介素1β（IL-1β）和白介素6（IL-6）的影响，但尚未确定邻近BMVEC在该调节中的作用，这是基础这项工作。结果我们提供了证据，表明人类BMVEC（hBMVEC）IL-1β和IL-6对邻近C6胶质瘤细胞（星形胶质细胞）的sCp转录表达有积极影响。通过添加IL-1β和IL-6途径抑制剂（分别为IL-1受体拮抗剂蛋白和SC144），抑制了hBMVEC在转录本和蛋白质水平上对C6胶质瘤sCp表达的影响。通过顶端暴露于细菌内毒素脂多糖刺激hBMVEC白介素基因表达可显着增强hBMVEC介导的C6胶质瘤sCp基因表达。结论hBMVEC影响邻近的C6神经胶质瘤sCp的基因表达。基因表达的这种改变是由hBMVEC分泌IL-1β和IL-6介导的。此外，hBMVEC诱导的邻近C6胶质瘤sCp基因表达的增加导致hBMVEC铁外排率增加。两者合计，我们的结果表明，hBMVEC分泌的细胞因子活性增加了邻近的C6胶质瘤sCp的基因表达，这反过来作用于基底外侧hBMVEC Fpn以增强脑铁的进口。

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