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氚水通过白细胞介素-8诱导人脐静脉血管内皮细胞毒性。

Tritiated Water Induces Toxicity in Human Umbilical Vein Vascular Endothelial Cells via IL8.

作者信息

Yan Hong-Bin, Liu Yi-Tong, Li Zhen-Yan, Wu Zhuo-Jun, Zhang Meng, Xue Pei-Jun, Liu Yu-Long, Wang Kong-Zhao, He Yong-Ming, Tu Yu, Cui Feng-Mei, Chen Qiu

机构信息

State Key Laboratory of Radiation Medicine and Protection, School of Radiation Medicine and Protection, Soochow University, Suzhou, People's Republic of China.

Collaborative Innovation Center of Radiation Medicine of Jiangsu Higher Education Institutions, Suzhou, People's Republic of China.

出版信息

Dose Response. 2020 Jul 7;18(3):1559325820938541. doi: 10.1177/1559325820938541. eCollection 2020 Jul-Sep.

Abstract

We aimed to determine the toxic effects of tritiated water (HTO) on 12 generations (T1-T12) of human umbilical vein vascular endothelial cells (HUVECs) and elucidate the underlying mechanisms. We evaluated cellular senescence, interleukin (IL) 8 concentrations, and angiogenesis using β-galactosidase staining, enzyme-linked immunosorbent assay, and in vitro assays, respectively. The adhesion properties of contaminated cells and differentially expressed genes were assessed using the xCELLigence RTCA SP system and gene chip analysis, respectively. We found that long-term exposure to low levels of HTO can reduce the adhesion of HUVECs to the cellular matrix as well as their angiogenic capacity, while increasing their permeability, senescence, and adhesion to monocytes. Interleukin 8 activated the p38 and Epidermal Growth Factor Receptor (EGFR) pathways in HTO-treated cells and hence was identified as a key candidate of biomarker. The present study clarified the toxicity of HTO in vascular endothelial cells and identified IL8 as a novel protective target with important theoretical and practical values.

摘要

我们旨在确定氚水(HTO)对人脐静脉血管内皮细胞(HUVECs)12代(T1-T12)的毒性作用,并阐明其潜在机制。我们分别使用β-半乳糖苷酶染色、酶联免疫吸附测定和体外试验评估细胞衰老、白细胞介素(IL)8浓度和血管生成。分别使用xCELLigence RTCA SP系统和基因芯片分析评估受污染细胞的黏附特性和差异表达基因。我们发现,长期暴露于低水平的HTO可降低HUVECs与细胞基质的黏附以及它们的血管生成能力,同时增加其通透性、衰老以及与单核细胞的黏附。白细胞介素8激活了HTO处理细胞中的p38和表皮生长因子受体(EGFR)途径,因此被确定为生物标志物的关键候选物。本研究阐明了HTO对血管内皮细胞的毒性,并确定IL8为具有重要理论和实践价值的新型保护靶点。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/15cc/7343372/05632295bfd4/10.1177_1559325820938541-fig1.jpg

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