Effects of interleukin-6 on the expression of tight junction proteins in isolated cerebral microvessels from yearling and adult sheep.
Effects of interleukin-6 on the expression of tight junction proteins in isolated cerebral microvessels from yearling and adult sheep.
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DOI：
10.1159/000350470
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发表时间：
2013
影响因子：
2.4
通讯作者：
Stonestreet BS
中科院分区：
文献类型：
--
作者：
Cohen SS;Min M;Cummings EE;Chen X;Sadowska GB;Sharma S;Stonestreet BS
血脑屏障是脑实质和血管内隔室之间的选择性扩散屏障。紧密连接（TJ）是血脑屏障的组成部分。促炎细胞因子在脑损伤的发病机制中起重要作用，并可改变TJ的蛋白质组成。我们假设IL-6下调内皮TJ的关键蛋白质成分（例如，封闭蛋白和封闭蛋白-5）。我们使用体外血脑屏障模型研究了IL-6对TJ蛋白表达的影响。我们从一岁和成年绵羊大脑皮层分离微血管，并将其置于IL-6浓度为0（对照，磷酸盐缓冲盐水），1，10和100 ng/mL的培养物中24小时。收获脑微血管，对闭合蛋白和密蛋白-5进行Western免疫印迹，进行密度测定，结果表示为与对照值的比率。Western免疫印迹分析显示，用100 ng/ml的IL-6处理，而不是较低浓度，降低（P <0.05）来自一岁和成年绵羊的微血管中的occludin表达，以及来自成年绵羊的微血管中的claudin-5。然而，用10 ng/ml的IL-6处理增加来自一岁绵羊的微血管中的claudin-5。从微血管释放到周围介质中的乳酸脱氢酶的百分比并没有增加IL-6治疗，表明TJ蛋白的减少并不导致细胞死亡。用与抗IL-6单克隆抗体预孵育的IL-6治疗成人大脑皮质微血管部分减弱了claudin-5的减少。我们的结论是，IL-6调节紧密连接蛋白的表达在大脑皮层微血管从一岁和成年绵羊。
The blood-brain barrier is a selective diffusion barrier between brain parenchyma and the intravascular compartment. Tight junctions (TJs) are integral components of the blood-brain barrier. Pro-inflammatory cytokines are important in the pathogenesis of brain injury and could modify the protein constituents of TJs. We hypothesized that IL-6 down-regulates key protein constituents of endothelial TJs (e.g., occludin and claudin-5). We examined the effects of IL-6 on TJ protein expression using an in vitro blood-brain barrier model. We isolated microvessels from yearling and adult ovine cerebral cortex and placed them into culture with IL-6 concentrations of 0 (control, phosphate buffered saline), 1, 10, and 100 ng/mL for 24 hours. Cerebral microvessels were harvested, Western immunoblot performed for occludin and claudin-5, densitometry performed, and results expressed as a ratio to control values. Western immunoblot analysis showed that treatment with 100 ng/ml of IL-6, but not the lower concentrations, reduced (P<0.05) occludin expression in microvessels from yearling and adult sheep, and claudin-5 in microvessels from adult sheep However, treatment with 10 ng/ml of IL-6 increased claudin-5 in microvessels from yearling sheep. The percent of lactate dehydrogenase released from the microvessels into the surrounding media was not increased by IL-6 treatment, suggesting that the reductions in TJ proteins did not result from cell death. Treatment of adult cerebral cortical microvessels with IL-6 pre-incubated with anti-IL-6 monoclonal antibodies partially attenuated the reduction in claudin-5. We conclude that IL-6 modulates tight junction protein expression in cerebral cortical microvessels from yearling and adult sheep.
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影响因子：
1.7
作者：
Gurkan OU;He C;Zielinski R;Rabb H;King LS;Dodd-o JM;D'Alessio FR;Aggarwal N;Pearse D;Becker PM
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Becker PM
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15.9
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