白细胞介素-6反式信号介导的人视网膜内皮细胞旁通透性调控

J. Glass, Rebekah Robinson, T. Lee, Ashok Sharma, Shruti Sharma
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引用次数: 2

摘要

长期高血糖介导的氧化应激和炎症导致血视网膜屏障(BRB)功能障碍和血管通透性增加,与糖尿病视网膜病变(DR)相关。白细胞介素-6 (IL-6)是视网膜血管炎症的主要介质之一。IL-6通过其膜结合IL-6受体的信号被称为经典信号,通过可溶性IL-6受体(sIL-6R)的信号被称为反式信号。越来越多的证据表明,经典信号主要是抗炎的,而反式信号则诱导IL-6的促炎作用。本研究的目的是比较这两种通路对人视网膜内皮细胞(HRECs)细胞旁通透性和内皮间连接相关基因表达的影响。IL-6反式信号激活对细胞旁完整性造成显著破坏,增加细胞旁通透性,并与粘附、紧密和间隙连接相关基因表达的显著变化相关。IL-6经典信号没有改变HRECs的细胞旁耐药,对基因表达也没有明显影响。总之,IL-6反式信号,而非经典信号,是糖尿病视网膜病变内BRB分解的细胞旁通透性增加特征的主要介质。本研究还发现了参与白细胞介素-6反式信号介导的HRECs细胞旁通透性调节的潜在内皮间连接基因。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
Interleukin-6 Trans-Signaling Mediated Regulation of Paracellular Permeability in Human Retinal Endothelial Cells
Long-term hyperglycemia-mediated oxidative stress and inflammation lead to the blood-retinal barrier (BRB) dysfunction and increased vascular permeability associated with diabetic retinopathy (DR). Interleukin-6 (IL-6) is one of the primary mediators of retinal vascular inflammation. IL-6 signaling through its membrane-bound IL-6 receptor is known as classical signaling, and through a soluble IL-6 receptor (sIL-6R) is known as trans-signaling. Increasing evidence suggests that classical signaling is primarily anti-inflammatory, whereas trans-signaling induces the pro-inflammatory effects of IL-6. The purpose of this study was to compare the effects of these two pathways on paracellular permeability and expression of genes involved in inter-endothelial junctions in human retinal endothelial cells (HRECs). IL-6 trans-signaling activation caused significant disruption to paracellular integrity, with increased paracellular permeability, and was associated with significant changes in gene expression related to adherens, tight, and gap junctions. IL-6 classical signaling did not alter paracellular resistance in HRECs and had no distinct effects on gene expression. In conclusion, IL-6 trans-signaling, but not classical signaling, is a major mediator of the increased paracellular permeability characteristic of inner BRB breakdown in diabetic retinopathy. This study also identified potential inter-endothelial junction genes involved in the IL-6 trans-signaling mediated regulation of paracellular permeability in HRECs.
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来源期刊
Journal of International Translational Medicine
Journal of International Translational Medicine MEDICINE, RESEARCH & EXPERIMENTAL-
自引率
0.00%
发文量
317
审稿时长
8 weeks
期刊介绍: Journal of International Translational Medicine (JITM, ISSN 2227-6394), founded in 2012, is an English academic journal published by Journal of International Translational Medicine Co., Ltd and sponsored by International Fderation of Translational Medicine. JITM is an open access journal freely serving to submit, review, publish, read and download full text and quote. JITM is a quarterly publication with the first issue published in March, 2013, and all articles published in English are compiled and edited by professional graphic designers according to the international compiling and editing standard. All members of the JITM Editorial Board are the famous international specialists in the field of translational medicine who come from twenty different countries and areas such as USA, Britain, France, Germany and so on.
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