FTY720 attenuates behavioral deficits in a murine model of systemic lupus erythematosus
FTY720 attenuates behavioral deficits in a murine model of systemic lupus erythematosus
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FTY720 减轻系统性红斑狼疮小鼠模型的行为缺陷
DOI：
10.1016/j.bbi.2018.03.009
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发表时间：
2018-05
期刊：
影响因子：
--
通讯作者：
Zhou Hong
中科院分区：
文献类型：
--
作者：
Shi Dongyan;Tian Tongguan;Yao Shu;Cao Kelei;Zhu Xingxing;Zhang Mingshun;Wen Shuang;Li Longjun;Shi Meiqing;Zhou Hong
神经精神病学（NP）介入系统性红斑狼疮（SLE）严重影响患者的生活质量，导致预后不良。目前的治疗方案，皮质类固醇管理，也可以诱发神经精神疾病。FTY720是一种免疫调节剂，选择性地限制淋巴结中的淋巴细胞，减少自身反应性T细胞向中枢神经系统（CNS）的募集。本研究旨在确定一种新的治疗NPSLE的策略。B6。用FTY720（2 mg/kg）口服MRL-lpr小鼠，每周3次，持续12 周，以评估其对NPSLE模型的疗效。FTY720显著减弱B6的冲动和抑郁样行为。MRL-lpr老鼠。fty720处理的B6的皮质、海马和杏仁核神经元损伤减轻。MRL-lpr小鼠，以及TNF-α-处理的HT22细胞。此外，FTY720下调炎症细胞因子水平，减少脑实质中T细胞和中性粒细胞的浸润。FTY720还直接作用于脑内皮细胞，降低B6血脑屏障（BBB）的通透性。MRL-lpr小鼠，中央IgG和白蛋白水平降低。最后，FTY720显著抑制PI3K/Akt/GSK3β/p65信号的激活，进一步降低bEND中粘附分子的表达水平。3个细胞用B6处理。MRL-lpr小鼠血清。总的来说，我们的数据表明，早期口服FTY720对npsle模型B6有有益的影响。MRL-lpr小鼠，提示它可能是一种有效的治疗NPSLE的新策略。
Neuropsychiatric (NP) involvement in systemic lupus erythematosus (SLE) severely impacts patients’ quality of life and leads to a poor prognosis. The current therapeutic protocol, corticosteroid administration, can also induce neuropsychiatric disorders. FTY720 is an immunomodulator that selectively confines lymphocytes in lymph nodes and reduces autoreactive T cell recruitment to the central nervous system (CNS). This study aimed to identify a novel therapeutic strategy for NPSLE. B6.MRL-lpr mice were treated with oral administration of FTY720 (2 mg/kg) three times per week for 12 weeks, to evaluate its efficacy in a model of NPSLE. FTY720 significantly attenuated the impulsive and depression-like behavior of B6.MRL-lpr mice. Neuronal damage was reduced in the cortex, hippocampus, and amygdala of the FTY720-treated B6.MRL-lpr mice, as well as in TNF-α-treated HT22 cells. Additionally, FTY720 downregulated levels of inflammatory cytokines, and reduced the infiltration of T cells and neutrophils in the brain parenchyma. FTY720 also acted directly on cerebral endothelial cells and reduced the permeability of the blood-brain barrier (BBB) in B6.MRL-lpr mice, as evidenced by reduced central IgG and albumin levels. Finally, FTY720 significantly inhibited activation of PI3K/Akt/GSK3β/p65 signaling, which further reduced the expression levels of adhesion molecules in bEND.3 cells treated with B6.MRL-lpr mouse serum. Collectively, our data indicate that oral administration of FTY720 at an early stage has beneficial effects in NPSLE-model B6.MRL-lpr mice, suggesting that it may represent an effective new therapeutic strategy for NPSLE.
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DOI：
10.1084/jem.20092210
发表时间：
2010-05-10
期刊：
The Journal of experimental medicine
影响因子：
--
作者：
Allende ML;Tuymetova G;Lee BG;Bonifacino E;Wu YP;Proia RL
通讯作者：
Proia RL
影响因子：
30.5
作者：
通讯作者：
--
DOI：
10.4049/jimmunol.182.2.1192
发表时间：
2009-01-15
期刊：
Journal of immunology (Baltimore, Md. : 1950)
影响因子：
--
作者：
Santer DM;Yoshio T;Minota S;Möller T;Elkon KB
通讯作者：
Elkon KB
影响因子：
7.3
作者：
Matsuoka, Y;Nagahara, Y;Shinomiya, T
通讯作者：
Shinomiya, T
DOI：
10.1016/s0140-6736(01)05732-4
发表时间：
2001-08
期刊：
The Lancet
影响因子：
--
作者：
P. Stratta;C. Canavese;S. Santi;G. Ciccone;S. Rosso
通讯作者：
P. Stratta;C. Canavese;S. Santi;G. Ciccone;S. Rosso