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首页> 外文期刊>Translational Stroke Research >Regulation of Toll-Like Receptors in the Choroid Plexus in the Immature Brain After Systemic Inflammatory Stimuli
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Regulation of Toll-Like Receptors in the Choroid Plexus in the Immature Brain After Systemic Inflammatory Stimuli

机译：全身性炎症刺激后未成熟大脑脉络丛中类似收费受体的调节

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The choroid plexus is the site of the blood–cerebrospinal fluid (CSF) barrier (BCSFB) and has also been considered as a possible route for peripheral immune signals and cells to transfer to the central nervous system. Infection/inflammation stimulates innate and subsequent adaptive immune responses via Toll-like receptors (TLRs). In this study, we have investigated the mRNA expression of TLRs, cytokines, and tight junction proteins in the choroid plexus in the immature brain after systemic inflammation, as well as accumulation of immune cells into the CSF. Specific ligands for TLR-1/2, TLR-3, and TLR-4 were administered to postnatal day8 mice and mRNA expression for the targeted genes was examined in the choroid plexus. We found that mRNA for all four TLRs was detected in the choroid plexus under control conditions. Following immune stimulation, expression of all the TLRs was upregulated by their respective ligands, except for TLR-4 mRNA, which was downregulated by Pam3CSK4 (PAM; a TLR-1/2 ligand). In addition, we investigated BCSFB regulation after TLR stimulation and found that TLR-1/2 and TLR-4 activation was associated with changes in mRNA expression of the tight junction protein occludin in the choroid plexus. PAM induced choroid plexus transcription of TNF-α and resulted in the most dramatic increase in numbers of white blood cells in the CSF. The data suggest a possible mechanism whereby systemic inflammation stimulates TLRs in the choroid plexus, which may lead to disturbances in choroid plexus barrier function, as well as infiltration of immune cells through the plexus.
机译：脉络丛是血脑脊液屏障（BCSFB）的部位，也被认为是外周免疫信号和细胞转移到中枢神经系统的可能途径。感染/炎症会通过Toll样受体（TLR）刺激先天和随后的适应性免疫反应。在这项研究中，我们研究了系统性炎症后未成熟大脑的脉络丛中TLRs，细胞因子和紧密连接蛋白的mRNA表达，以及免疫细胞向CSF的积累。将TLR-1 / 2，TLR-3和TLR-4的特异性配体施用于出生后的第8天小鼠，并检查脉络丛中靶基因的mRNA表达。我们发现在控制条件下脉络丛中检测到所有四个TLR的mRNA。免疫刺激后，除TLR-4 mRNA外，所有TLR的表达均被其各自的配体上调，TLR-4 mRNA被Pam3CSK4（PAM； TLR-1 / 2配体）下调。此外，我们研究了TLR刺激后BCSFB的调节，发现TLR-1 / 2和TLR-4激活与脉络丛中紧密连接蛋白occludin mRNA表达的变化有关。 PAM诱导了TNF-α的脉络丛神经转录，并导致CSF中白细胞数量的增加最为明显。数据提示全身性炎症刺激脉络丛神经中的TLR，这可能导致脉络丛神经屏障功能紊乱以及免疫细胞通过神经丛浸润。

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