Markedly increased IP-10 production by blood-brain barrier in neuromyelitis optica.
Markedly increased IP-10 production by blood-brain barrier in neuromyelitis optica.
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DOI：
10.1371/journal.pone.0122000
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发表时间：
2015
期刊：
影响因子：
3.7
通讯作者：
Kanda T
中科院分区：
文献类型：
--
作者：
Shimizu F;Nishihara H;Sano Y;Takeshita Y;Takahashi S;Maeda T;Takahashi T;Abe M;Koga M;Kanda T
在视神经脊髓炎(NMO)患者中，血脑屏障(BBB)的严重破坏使得抗水通道蛋白4(AQP4)抗体能够进入星形细胞终末。在目前的研究中，我们确定了致病细胞因子/趋化因子导致NMO血清诱导的BBB功能障碍。用多重荧光微珠免疫分析系统检测了抗AQP4抗体阳性NMO谱系障碍(NMOSD)急性期和稳定期患者、多发性硬化症(MS)患者和健康对照(HC)患者血清作用后人脑微血管内皮细胞(BMECs)中27种细胞因子/趋化因子的水平。NMOSD急性期血清暴露后，细胞内诱导蛋白(IP)-10水平明显升高。其他细胞因子/趋化因子包括白介素6和单核细胞趋化蛋白1在急性NMOSD组也显著高于MS组和HC组。用另一种特定的酶联免疫吸附试验也观察到，在暴露于急性期NMOSD血清后，细胞中IP-10水平的上调，在NMOSD患者的缓解期，这种影响显著降低。此外，暴露于血清后IP-10水平的升高与脑脊液/血清白蛋白比率显著相关。NMO急性期血清可显著促进BMECs自分泌IP-10。BMECs中IP-10的过度产生可能在NMO的发病机制中起重要作用，从而可能有助于介导表达其受体的T细胞跨血脑屏障的转运。
Severe damage to the blood-brain barrier (BBB) allows anti-aquaporin 4 (AQP4) antibodies to access the astrocytic endfeet in neuromyelitis optica (NMO). In the current study, we identified the pathogenic cytokines/chemokines that are responsible for the BBB malfunction induced by NMO sera. We measured the levels of 27 cytokines/chemokines in human brain microvascular endothelial cells (BMECs) after exposure to sera obtained from patients with the acute and stable phases of anti-AQP4 antibody-positive NMO spectrum disorder (NMOSD), multiple sclerosis (MS) patients and healthy controls (HC) using a multiplexed fluorescent bead-based immunoassay system. The induced protein (IP)-10 level in the cells was markedly increased following exposure to acute phase NMOSD sera. Other cytokines/chemokines including interleukin (IL)-6 and monocyte chemotactic protein (MCP)-1 were also significantly increased in the acute NMOSD group compared to both the MS and HC groups. The up-regulation of the IP-10 levels in the cells after exposure to the acute-phase NMOSD sera was also observed using another specified ELISA, and this effect was significantly decreased during the remission phase in the individual NMOSD patients. Furthermore, the increase in the level of IP-10 after exposure to the sera was significantly correlated with the cerebrospinal fluid/serum albumin ratio. Sera from the acute phase of NMO markedly increased the autocrine secretion of IP-10 by BMECs. The over-production of IP-10 in BMECs may play an important role in the pathogenesis of NMO and may therefore help to mediate the trafficking of T cells expressing its receptor across the BBB.
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影响因子：
3.7
作者：
Matsushita T;Tateishi T;Isobe N;Yonekawa T;Yamasaki R;Matsuse D;Murai H;Kira J
通讯作者：
Kira J
纹状体内注射白介素-1ββ触发了NMO-IGG血清阳性大鼠的神经霉素类似神经瘤性病变的形成。
影响因子：
7.1
作者：
Kitic M;Hochmeister S;Wimmer I;Bauer J;Misu T;Mader S;Reindl M;Fujihara K;Lassmann H;Bradl M
通讯作者：
Bradl M
DOI：
10.1016/s1474-4422(12)70133-3
发表时间：
2012-06
期刊：
The Lancet. Neurology
影响因子：
--
作者：
Papadopoulos MC;Verkman AS
通讯作者：
Verkman AS
影响因子：
2.2
作者：
Icoz, Sema;Tuzun, Erdem;Akman-Demir, Guelsen
通讯作者：
Akman-Demir, Guelsen
DOI：
10.1111/bpa.12099
发表时间：
2014-01
期刊：
Brain pathology (Zurich, Switzerland)
影响因子：
--
作者：
Lucchinetti CF;Guo Y;Popescu BF;Fujihara K;Itoyama Y;Misu T
通讯作者：
Misu T