IL-10 Promotes Neurite Outgrowth and Synapse Formation in Cultured Cortical Neurons after the Oxygen-Glucose Deprivation via JAK1/STAT3 Pathway
IL-10 Promotes Neurite Outgrowth and Synapse Formation in Cultured Cortical Neurons after the Oxygen-Glucose Deprivation via JAK1/STAT3 Pathway
复制标题
IL-10 通过 JAK1/STAT3 途径促进缺氧-葡萄糖剥夺后培养的皮质神经元中的神经突生长和突触形成
DOI：
10.1038/srep30459
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发表时间：
2016-07-26
影响因子：
4.6
通讯作者：
Liu, Nan
中科院分区：
文献类型：
--
作者：
Chen, Hongbin;Lin, Wei;Liu, Nan
白细胞介素-10（IL-10）作为一种经典的免疫调节和抗炎细胞因子，在体外对脑缺血或氧糖剥夺（OGD）诱导的脑损伤具有神经保护作用。然而，IL-10是否促进OGD损伤后培养的原代皮层神经元的轴突生长和突触形成仍不清楚。为了评价其对神经元凋亡、轴突生长和突触形成的影响，我们在OGD损伤后给予培养的大鼠原代皮层神经元IL-10或IL-10中和抗体（IL-10 NA）。我们发现IL-10处理激活了Janus激酶1（JAK 1）/信号转导和转录激活因子3（STAT 3）信号通路。此外，IL-10通过下调Bax表达和上调Bcl-2表达减轻OGD诱导的神经元凋亡，通过增加Netrin-1的表达促进轴突生长，并促进OGD损伤后原代培养的皮层神经元突触形成。JAK 1抑制剂GLPG 0634可部分阻断上述作用。而IL-10 NA对OGD损伤后培养的皮层神经元则产生相反的作用。总之，我们的研究结果表明，IL-10不仅减弱神经元凋亡，而且还通过JAK 1/STAT 3信号通路促进培养的原代皮层神经元OGD损伤后的轴突生长和突触形成。
As a classic immunoregulatory and anti-inflammatory cytokine, interleukin-10 (IL-10) provides neuroprotection in cerebral ischemiain vivoor oxygen-glucose deprivation (OGD)-induced injuryin vitro. However, it remains blurred whether IL-10 promotes neurite outgrowth and synapse formation in cultured primary cortical neurons after OGD injury. In order to evaluate its effect on neuronal apoptosis, neurite outgrowth and synapse formation, we administered IL-10 or IL-10 neutralizing antibody (IL-10NA) to cultured rat primary cortical neurons after OGD injury. We found that IL-10 treatment activated the Janus kinase 1 (JAK1)/signal transducers and activators of transcription 3 (STAT3) signaling pathway. Moreover, IL-10 attenuated OGD-induced neuronal apoptosis by down-regulating the Bax expression and up-regulating the Bcl-2 expression, facilitated neurite outgrowth by increasing the expression of Netrin-1 and promoted synapse formation in cultured primary cortical neurons after OGD injury. These effects were partly abolished by JAK1 inhibitor GLPG0634. Contrarily, IL-10NA produced opposite effects on the cultured cortical neurons after OGD injury. Taken together, our findings suggest that IL-10 not only attenuates neuronal apoptosis, but also promotes neurite outgrowth and synapse formation via the JAK1/STAT3 signaling pathway in cultured primary cortical neurons after OGD injury.