Alpha-1 Antitrypsin Attenuates M1 Microglia-Mediated Neuroinflammation in Retinal Degeneration.
Alpha-1 Antitrypsin Attenuates M1 Microglia-Mediated Neuroinflammation in Retinal Degeneration.
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Alpha-1 抗胰蛋白酶可减轻视网膜变性中 M1 小胶质细胞介导的神经炎症
DOI：
10.3389/fimmu.2018.01202
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发表时间：
2018
影响因子：
7.3
通讯作者：
Liu X
中科院分区：
文献类型：
--
作者：
Zhou T;Huang Z;Zhu X;Sun X;Liu Y;Cheng B;Li M;Liu Y;He C;Liu X
神经退行性疾病是一组以进行性神经元死亡为特征的疾病，与小胶质细胞介导的神经炎症有关。最近，提出神经炎症是许多神经退行性疾病的有前途的治疗靶点。 α-1抗胰蛋白酶（AAT）被认为是自身免疫性疾病和移植中的一种新型免疫调节剂，但是，其对神经炎症和神经变性的影响仍然未知。这项研究旨在探索AAT对RD1小鼠模型中小胶质细胞介导的神经炎症和视网膜变性的影响。我们发现AAT在RD1视网膜中的表达降低，AAT补充剂对视网膜变性表现出一定的保护作用，表现出增加的光感受器核的量增加，并且在电视图分析中显示了放大的波幅度。值得注意的是，AAT将小胶质细胞表型从促炎的M1（CD16/CD32+，iNOS+）转移到体内和体外的抗炎M2（CD206+，ARG1+）的抗炎M2（CD206+，ARG1+），强调了在NeuroDegeneration期间AAT对微胶质细胞化的免疫调节的概念。此外，AAT抑制了STAT1的激活，在抑制IRF8表达的同时促进了IRF4的表达，表明这些信号传导途径参与AAT免疫调节。总的来说，我们的数据为通过对小胶质细胞化的免疫调节提供了AAT新型保护作用的证据。 AAT通过AAT衰减神经炎症可能有益于RD1小鼠中的神经变性。
Neurodegenerative diseases are a set of disorders characterized by progressive neuronal death and are associated with microglia-mediated neuroinflammation. Recently, neuroinflammation is proposed as a promising therapeutic target for many neurodegenerative diseases. Alpha-1 antitrypsin (AAT) is recognized as a novel immunomodulatory agent in autoimmune diseases and transplantation, however, its impact on neuroinflammation and neurodegeneration remains unknown. This study aims to explore the effects of AAT on microglia-mediated neuroinflammation and retinal degeneration in rd1 mouse model. We found reduced expression of AAT in rd1 retina, and AAT supplement exhibited certain protective effect on retinal degeneration, presenting with increased amount of photoreceptor nuclei, and amplified wave amplitudes in electroretinogram analysis. Of note, AAT shifted microglia phenotype from pro-inflammatory M1 (CD16/CD32+, iNOS+) to anti-inflammatory M2 (CD206+, Arg1+) both in vivo and in vitro, underscoring the concept of immunomodulation on microglia polarization by AAT during neurodegeneration. Furthermore, AAT suppressed the activation of STAT1, promoted the expression of IRF4 while inhibited IRF8 expression, indicating the involvement of these signaling pathways in AAT immunomodulation. Collectively, our data provided evidence for a novel protective role of AAT through immunomodulation on microglia polarization. Attenuating neuroinflammation by AAT may be beneficial to retard neurodegeneration in rd1 mice.
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影响因子：
20.3
作者：
Marcondes, A. Mario;Karoopongse, Ekapun;Deeg, H. Joachim
通讯作者：
Deeg, H. Joachim
小胶质细胞坏死性凋亡通过 TLR4 激活导致神经炎症和视网膜变性
影响因子：
12.4
作者：
Huang Z;Zhou T;Sun X;Zheng Y;Cheng B;Li M;Liu X;He C
通讯作者：
He C
影响因子：
13.7
作者：
Pierrache LHM;Kimchi A;Ratnapriya R;Roberts L;Astuti GDN;Obolensky A;Beryozkin A;Tjon-Fo-Sang MJH;Schuil J;Klaver CCW;Bongers EMHF;Haer-Wigman L;Schalij N;Breuning MH;Fischer GM;Banin E;Ramesar RS;Swaroop A;van den Born LI;Sharon D;Cremers FPM
通讯作者：
Cremers FPM
影响因子：
30.5
作者：
Satoh, Takashi;Takeuchi, Osamu;Akira, Shizuo
通讯作者：
Akira, Shizuo
DOI：
10.1073/pnas.0505579102
发表时间：
2005-08-23
影响因子：
11.1
作者：
Lewis, EC;Shapiro, L;Dinarello, CA
通讯作者：
Dinarello, CA