IL-17A Neutralization Improves the Neurological Outcome of Mice With Ischemic Stroke and Inhibits Caspase-12-Dependent Apoptosis.
IL-17A Neutralization Improves the Neurological Outcome of Mice With Ischemic Stroke and Inhibits Caspase-12-Dependent Apoptosis.
复制标题
IL-17A 中和可改善缺血性中风小鼠的神经学结果并抑制 Caspase-12 依赖性细胞凋亡
DOI：
10.3389/fnagi.2020.00274
复制
发表时间：
2020
影响因子：
4.8
通讯作者：
Li S
中科院分区：
文献类型：
--
作者：
Dai Q;Han S;Liu T;Zheng J;Liu C;Li J;Li S
我们以前报道过，星形胶质细胞衍生的白细胞介素-17A（IL-17 A）的水平增加，无论是在梗死周围区域和脑脊液（CSF）的小鼠与1小时大脑中动脉（MCA）闭塞/12小时再灌注（1小时MCAO/R 12小时）诱导的缺血性中风。然而，IL-17 A中和对缺血性卒中小鼠神经学结局的影响及其潜在的分子机制尚不清楚。在本研究中，我们发现侧脑室注射IL-17 A中和性单克隆抗体（mAb; 2.0 μg）可以减少MCAO/R 1-h 24-h或3-d诱导的缺血-卒中小鼠的梗死体积，减轻神经元丢失，并改善神经功能结局。IL-17 A中和还可以通过caspase-12依赖性细胞凋亡显著抑制caspase-3前体切割的增加，以及防止缺血性卒中后小鼠梗死周围区域中抗凋亡因子B细胞淋巴瘤2（Bcl-2）的减少和促凋亡Bcl-2相关X蛋白（Bax）的增加。此外，我们证实rmIL-17 A可剂量依赖性地加重1 h OGD/R 24 h诱导的皮层神经元缺血性损伤，rmIL-17 A还可通过caspase-12（而非caspase-8或caspase-9）依赖性途径加重神经元凋亡。这些结果表明，IL-17 A中和可以通过抑制caspase-12依赖的神经元凋亡来改善缺血性卒中小鼠的神经功能结局。
We previously reported that the levels of astrocyte-derived interleukin-17A (IL-17A) increased both in the peri-infarct region and cerebrospinal fluid (CSF) of mice with 1-h middle cerebral artery (MCA) occlusion/12-h reperfusion (1-h MCAO/R 12 h)-induced ischemic stroke. However, the effects of IL-17A neutralization on the neurological outcome of mice with ischemic stroke and its underlying molecular mechanism are unclear. In this study, we found that the intracerebroventricular injection of IL-17A-neutralizing monoclonal antibody (mAb; 2.0 μg) could reduce the infarct volume, alleviate neuron loss, and improve the neurological outcomes of mice with 1-h MCAO/R 24-h- or 3-day-induced ischemic-stroke mice. The IL-17A neutralization could also significantly inhibit the increase of pro-caspase-3 cleavage through caspase-12-dependent cell apoptosis, as well as preventing the decrease of antiapoptotic factor B-cell lymphoma 2 (Bcl-2) and the increase of proapoptotic Bcl-2-associated X protein (Bax) in the peri-infarct region of mice following ischemic stroke. In addition, we confirmed that the recombinant mouse (rm) IL-17A could significantly aggravate 1-h oxygen–glucose deprivation/24-h reoxygenation (1-h OGD/R 24 h)-induced ischemic injuries in cortical neurons in a dose-dependent manner, and the rmIL-17A could also exacerbate neuronal apoptosis through caspase-12 (not caspase-8 or caspase-9)-dependent pathway. These results suggest that IL-17A neutralization could improve the neurological outcome of mice with ischemic stroke through inhibiting caspase-12-dependent neuronal apoptosis.
登录
查看更多内容
影响因子：
3
作者：
Rodriguez, R;Santiago-Mejia, J;San-Juan, ER
通讯作者：
San-Juan, ER
影响因子：
20.3
作者：
Gelderblom, Mathias;Weymar, Anna;Magnus, Tim
通讯作者：
Magnus, Tim
影响因子：
3.7
作者：
Li, GZ;Zhong, D;Li, HL
通讯作者：
Li, HL
低剂量的 Apelin-36 可减弱缺血性中风大鼠内质网应激相关的细胞凋亡。
影响因子：
3.4
作者：
Qiu J;Wang X;Wu F;Wan L;Cheng B;Wu Y;Bai B
通讯作者：
Bai B
影响因子：
3.7
作者：
Li X;Wang MH;Qin C;Fan WH;Tian DS;Liu JL
通讯作者：
Liu JL