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.
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July 2017
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A 3D optical coherence tomography image of the retina. In this issue, Long et al, investigated a unique sample of human infants with bilateral cataract and deciphered the role of the retina in visual system development and plasticity. For further details, please see article by Lin et al, in this issue. Image kindly provided by Haotian Lin.
Research Article|
June 28 2017
Exacerbation of oxygen–glucose deprivation-induced blood–brain barrier disruption: potential pathogenic role of interleukin-9 in ischemic stroke
Sha Tan;
Sha Tan
*
1Department of Neurology, The Third Affiliated Hospital of Sun Yat-sen University, No. 600 Tianhe Road, Guangzhou, China
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Yilong Shan;
Yilong Shan
*
1Department of Neurology, The Third Affiliated Hospital of Sun Yat-sen University, No. 600 Tianhe Road, Guangzhou, China
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Yuge Wang;
Yuge Wang
*
1Department of Neurology, The Third Affiliated Hospital of Sun Yat-sen University, No. 600 Tianhe Road, Guangzhou, China
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Yinyao Lin;
Yinyao Lin
1Department of Neurology, The Third Affiliated Hospital of Sun Yat-sen University, No. 600 Tianhe Road, Guangzhou, China
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Siyuan Liao;
Siyuan Liao
1Department of Neurology, The Third Affiliated Hospital of Sun Yat-sen University, No. 600 Tianhe Road, Guangzhou, China
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Zhezhi Deng;
Zhezhi Deng
1Department of Neurology, The Third Affiliated Hospital of Sun Yat-sen University, No. 600 Tianhe Road, Guangzhou, China
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Li Zhou;
Li Zhou
1Department of Neurology, The Third Affiliated Hospital of Sun Yat-sen University, No. 600 Tianhe Road, Guangzhou, China
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Wei Cai;
Wei Cai
1Department of Neurology, The Third Affiliated Hospital of Sun Yat-sen University, No. 600 Tianhe Road, Guangzhou, China
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Qin Zeng;
Qin Zeng
1Department of Neurology, The Third Affiliated Hospital of Sun Yat-sen University, No. 600 Tianhe Road, Guangzhou, China
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Lei Zhang;
Lei Zhang
2Department of Neurology, The Fifth Affiliated Hospital of Sun Yat-sen University, No. 52 Mei Hua East Road, Zhuhai, China
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Bingjun Zhang;
Bingjun Zhang
1Department of Neurology, The Third Affiliated Hospital of Sun Yat-sen University, No. 600 Tianhe Road, Guangzhou, China
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Xuejiao Men;
Xuejiao Men
1Department of Neurology, The Third Affiliated Hospital of Sun Yat-sen University, No. 600 Tianhe Road, Guangzhou, China
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Haiyan Li;
Haiyan Li
1Department of Neurology, The Third Affiliated Hospital of Sun Yat-sen University, No. 600 Tianhe Road, Guangzhou, China
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Xueqiang Hu;
Xueqiang Hu
1Department of Neurology, The Third Affiliated Hospital of Sun Yat-sen University, No. 600 Tianhe Road, Guangzhou, China
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Changyou Wu;
Changyou Wu
3Guangdong Provincial Key Laboratory of Organ Donation and Transplant Immunology, Institute of Immunology, Zhongshan School of Medicine, Sun Yat-sen University, No. 74, Zhongshan 2nd Road, Guangzhou, China
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Lisheng Peng;
1Department of Neurology, The Third Affiliated Hospital of Sun Yat-sen University, No. 600 Tianhe Road, Guangzhou, China
Correspondence: Zhengqi Lu ([email protected]) or Lisheng Peng ([email protected])
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Zhengqi Lu
1Department of Neurology, The Third Affiliated Hospital of Sun Yat-sen University, No. 600 Tianhe Road, Guangzhou, China
Correspondence: Zhengqi Lu ([email protected]) or Lisheng Peng ([email protected])
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Publisher: Portland Press Ltd
Received:
April 17 2017
Revision Received:
May 24 2017
Accepted:
May 26 2017
Accepted Manuscript online:
May 26 2017
Online ISSN: 1470-8736
Print ISSN: 0143-5221
© 2017 The Author(s). Published by Portland Press Limited on behalf of the Biochemical Society
2017
Clin Sci (Lond) (2017) 131 (13): 1499–1513.
Article history
Received:
April 17 2017
Revision Received:
May 24 2017
Accepted:
May 26 2017
Accepted Manuscript online:
May 26 2017
Citation
Sha Tan, Yilong Shan, Yuge Wang, Yinyao Lin, Siyuan Liao, Zhezhi Deng, Li Zhou, Wei Cai, Qin Zeng, Lei Zhang, Bingjun Zhang, Xuejiao Men, Haiyan Li, Xueqiang Hu, Changyou Wu, Lisheng Peng, Zhengqi Lu; Exacerbation of oxygen–glucose deprivation-induced blood–brain barrier disruption: potential pathogenic role of interleukin-9 in ischemic stroke. Clin Sci (Lond) 1 July 2017; 131 (13): 1499–1513. doi: https://doi.org/10.1042/CS20170984
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