Exacerbation of oxygen-glucose deprivation-induced blood-brain barrier disruption: potential pathogenic role of interleukin-9 in ischemic stroke
Exacerbation of oxygen-glucose deprivation-induced blood-brain barrier disruption: potential pathogenic role of interleukin-9 in ischemic stroke
复制标题
氧糖剥夺引起的血脑屏障破坏加剧：白细胞介素 9 在缺血性中风中的潜在致病作用
DOI：
10.1042/cs20170984
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发表时间：
2017-07-01
期刊：
影响因子：
6
通讯作者：
Lu, Zhengqi
中科院分区：
文献类型：
--
作者：
Tan, Sha;Shan, Yilong;Lu, Zhengqi
Interleukin (IL)-9 exerts a variety of functions in autoimmune diseases. However, its role in ischemic brain injury remains unknown. The present study explored the biological effects of IL-9 in ischemic stroke (IS). We recruited 42 patients newly diagnosed with IS and 22 age-and sex-matched healthy controls. The expression levels of IL-9 and percentages of IL-9-producing T cells, including CD3(+)CD4(+)IL-9(+) and CD3(+)CD8(+)IL-9(+) cells, were determined in peripheral blood mononuclear cells (PBMCs) obtained from patients and control individuals. We also investigated the effects of IL-9 on the blood-brain barrier (BBB) following oxygen-glucose deprivation (OGD) and the potential downstream signaling pathways. We found that patients with IS had higher IL-9 expression levels and increased percentages of IL-9-producing T cells in their PBMCs. The percentages of CD3(+)CD4(+)IL-9(+) and CD3(+)CD8(+)IL-9(+) T cells were positively correlated with the severity of illness. In in vitro experiments using bEnd.3 cells, exogenously administered IL-9 exacerbated the loss of tight junction proteins (TJPs) in cells subjected to OGD plus reoxygenation (RO). This effect was mediated via activation of IL-9 receptors, which increased the level of endothelial nitric oxide synthase (eNOS), as well as through up-regulated phosphorylation of signal transducer and activator of transcription 1 and 3 and down-regulated phosphorylated protein kinase B/phosphorylated phosphatidylinositol 3-kinase signaling. These results indicate that IL-9 has a destructive effect on the BBB following OGD, at least in part by inducing eNOS production, and raise the possibility of targetting IL-9 for therapeutic intervention in IS.
