Exacerbation of oxygen-glucose deprivation-induced blood brain barrier disruption: potential pathogenic role of interleukin 9 in ischemic stroke

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. We recruited 42 patients newly diagnosed with ischemic stroke 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 and the potential downstream signaling pathways. We found that patients with ischemic stroke 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 invitro experiments using bEnd.3 cells, exogenously administered IL-9 exacerbated the loss of tight junction proteins in cells subjected to oxygen-glucose deprivation plus reoxygenation. This effect was mediated via activation of IL-9 receptors, which increased the level of endothelial nitric oxide synthase (eNOS), as well as through upregulated phosphorylation of signal transducer and activator of transcription 1 and 3 and downregulated phosphorylated protein kinase B/phosphorylated phosphatidylinositol 3-kinase sign...

Source: Clinical Science - May 26, 2017 Category: Biomedical Science Authors: Tan, S., Shan, Y., Wang, Y., Lin, Y., Liao, S., Deng, Z., Zhou, L., Cai, W., Zeng, Q., Zhang, L., Zhang, B., Men, X., Li, H., Hu, X., Wu, C., Peng, L., Lu, Z. Tags: PublishAheadOfPrint Source Type: research