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Endosulfan induces endothelial inflammation and dysfunction via IRE1α/NF-κB signaling pathway

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Abstract

Cardiovascular diseases are related to vascular endothelial cell injury; our previous studies showed that endosulfan could cause hypercoagulation of blood by inducing endothelial cell injury. To clarify the mechanism of it, we treated human umbilical vein endothelial cells (HUVECs) with 0, 1, 5, and 10 μg/mL endosulfan, while in the inhibition groups, reactive oxygen species (ROS) inhibitor N-acetylcysteine (NAC, 3 mmol) and endoplasmic reticulum (ER) stress inhibitor (STF-083010, 10 μmol) were incubated prior to endosulfan. The results showed that endosulfan could induce inflammatory response and dysfunction by increasing the release of inflammatory cytokines such as interleukin-1β (IL-1β), interleukin-6 (IL-6), tumor necrosis factor alpha (TNF-α), and adhesion molecules such as vascular cell adhesion molecule 1 (VCAM-1) and endothelin-1 (ET-1), and inducing ROS production in HUVECs. We also found that endosulfan could cause ER damage, remarkably increase the expressions of inositol-requiring enzyme 1α (IRE1α), phosphorylated IRE1α (p-IRE1α), GRP78, XBP1, nuclear factor-kappa B (NF-κB), and phosphorylated NF-κB (p-NF-κB) in HUVECs. The presence of NAC antagonized the ROS production, expressions of IRE1α and p-IRE1α; however, STF-083010 could decrease the expression levels of GRP78, XBP1, NF-κB, and p-NF-κB and attenuate IL-1β, IL-6, TNF-α, VCAM-1, and ET-1 release induced by endosulfan. These results demonstrated that endosulfan-induced endothelial inflammation and dysfunction through the IRE1α/NF-κB signaling pathway may be triggered by oxidative stress. The study provided experimental basis for the correlation between environmental pollutants (endosulfan) and cardiovascular diseases.

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Funding

This study was supported by the Nature Science Foundation from Shandong Province (No. ZR2016HL24).

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Author notes

  1. ShiTian Sun and ZhengGuo Ji contributed equally to this work.

Authors and Affiliations

  1. College of Clinical Medicine, Binzhou Medical University, Yantai, People’s Republic of China

    ShiTian Sun & JiaRong Fu

  2. Department of Urology, Beijing Friendship Hospital, Capital medical University, Beijing, China

    ZhengGuo Ji

  3. Department of Critical Care Medicine, Yu Huang Ding Hospital, Qingdao University, Yantai, 264000, People’s Republic of China

    Xi-Feng Wang

  4. Department of Histology and Embryology, Binzhou Medical University, Yantai, 264003, People’s Republic of China

    Lian-Shuang Zhang

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  1. ShiTian Sun
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  2. ZhengGuo Ji
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  4. Xi-Feng Wang
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Correspondence to Xi-Feng Wang or Lian-Shuang Zhang.

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Responsible editor: Philippe Garrigues

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Sun, S., Ji, Z., Fu, J. et al. Endosulfan induces endothelial inflammation and dysfunction via IRE1α/NF-κB signaling pathway. Environ Sci Pollut Res 27, 26163–26171 (2020). https://doi.org/10.1007/s11356-020-09023-5

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  • DOI: https://doi.org/10.1007/s11356-020-09023-5

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