Lin Longzai, Chen Hongbin, Zhang Yixian, Lin Wei, Liu Yong, Li Tin, Zeng Yongping, Chen Jianhao, Du Houwei, Chen Ronghua, Tan Yi, Liu Nan
Department of Neurology, The Affiliated Union Hospital, Fujian Medical University, Fuzhou, Fujian, People's Republic of China; Institute of Cerebral Vascular Disease of Fujian Province, Fuzhou, Fujian, People's Republic of China.
Institute of Cerebral Vascular Disease of Fujian Province, Fuzhou, Fujian, People's Republic of China; Department of Rehabilitation, The Affiliated Union Hospital, Fujian Medical University, Fuzhou, Fujian, People's Republic of China.
PLoS One. 2015 Sep 14;10(9):e0136959. doi: 10.1371/journal.pone.0136959. eCollection 2015.
IL-10, as a cytokine, has an anti-inflammatory cascade following various injuries, but it remains blurred whether IL-10 protects neurites of cortical neurons after oxygen-glucose deprivation injury. Here, we reported that IL-10, in a concentration-dependent manner, reduced neuronal apoptosis and increased neuronal survival in oxygen-glucose-deprived primary cortical neurons, producing an optimal protective effect at 20ng/ml. After staining NF-H and GAP-43, we found that IL-10 significantly protected neurites in terms of axon length and dendrite number by confocal microscopy. Furthermore, it induced the phosphorylation of AKT, suppressed the activation of caspase-3, and up-regulated the protein expression of GAP-43. In contrast, LY294002, a specific inhibitor of PI3K/AKT, reduced the level of AKT phosphorylation and GAP-43 expression, increased active caspase-3 expression and thus significantly weakened IL-10-mediated protective effect in the OGD-induced injury model. IL-10NA, the IL-10 neutralizing antibody, reduced the level of p-PI3K phosphorylation and increased the expression of active caspase-3. These findings suggest that IL-10 provides neuroprotective effects by protecting neurites through PI3K/AKT signaling pathway in oxygen-glucose-deprived primary cortical neurons.
白细胞介素-10（IL-10）作为一种细胞因子，在各种损伤后具有抗炎级联反应，但IL-10在氧糖剥夺损伤后是否能保护皮质神经元的神经突仍不清楚。在此，我们报告IL-10以浓度依赖的方式减少氧糖剥夺的原代皮质神经元中的神经元凋亡并增加神经元存活，在20ng/ml时产生最佳保护作用。在用神经丝蛋白-H（NF-H）和生长相关蛋白43（GAP-43）染色后，我们通过共聚焦显微镜发现IL-10在轴突长度和树突数量方面显著保护了神经突。此外，它诱导了蛋白激酶B（AKT）的磷酸化，抑制了半胱天冬酶-3（caspase-3）的激活，并上调了GAP-43的蛋白表达。相比之下，磷脂酰肌醇-3激酶（PI3K）/AKT的特异性抑制剂LY294002降低了AKT磷酸化水平和GAP-43表达，增加了活性caspase-3的表达，从而在氧糖剥夺诱导的损伤模型中显著削弱了IL-10介导的保护作用。IL-10中和抗体IL-10NA降低了磷酸化PI3K（p-PI3K）的水平，并增加了活性caspase-3的表达。这些发现表明，在氧糖剥夺的原代皮质神经元中，IL-10通过PI3K/AKT信号通路保护神经突，从而发挥神经保护作用。
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