Luteolin Inhibits Indoxyl Sulfate-Induced ICAM-1 and MCP-1 Expression by Inducing HO-1 Expression in EA.hy926 Human Endothelial Cells

IF 4.4 3区医学 Q2 ENVIRONMENTAL SCIENCES Environmental Toxicology Pub Date : 2024-08-06 DOI:10.1002/tox.24380

Li-Chien Chang, En-Ling Yeh, Ya-Chi Chuang, Chia-Hsuan Wu, Chia-Wen Kuo, Chong-Kuei Lii, Ya-Chen Yang, Haw-Wen Chen, Chien-Chun Li

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Abstract

In patients with chronic kidney disease, the uremic toxin indoxyl sulfate (IS) accelerates kidney damage and the progression of cardiovascular disease. IS may contribute to vascular diseases by inducing inflammation in endothelial cells. Luteolin has documented antioxidant and anti-inflammatory properties. This study aimed to investigate the effect of luteolin on IS-mediated reactive oxygen species (ROS) production and intercellular adhesion molecule (ICAM-1) and monocyte chemoattractant protein (MCP-1) expression in EA.hy926 cells and the possible mechanisms involved. IS significantly induced ROS production (by 6.03-fold, p < 0.05), ICAM-1 (by 2.19-fold, p < 0.05) and MCP-1 protein expression (by 2.18-fold, p < 0.05), and HL-60 cell adhesion (by 31%, p < 0.05), whereas, luteolin significantly decreased IS-induced ROS production, ICAM-1 and MCP-1 protein expression, and HL-60 cell adhesion. Moreover, luteolin attenuated IS-induced nuclear accumulation of p65 and c-jun. Luteolin dose-dependently increased heme oxygenase-1 (HO-1) expression and the maximum fold induction of HO-1 by luteolin was 3.68-fold (p < 0.05), whereas, HO-1 knockdown abolished the suppression of ICAM-1 and MCP-1 expression by luteolin. Luteolin may protect against IS-induced vessel damage by inducing HO-1 expression in vascular endothelial cells, which suppresses nuclear factor kappa B (NF-κB) and activator protein 1 (AP-1) mediated ICAM-1 and MCP-1 expression.

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木犀草素通过诱导 EA.hy926 人内皮细胞中 HO-1 的表达抑制硫酸吲哚啉诱导的 ICAM-1 和 MCP-1 表达

在慢性肾病患者中，尿毒症毒素硫酸吲哚乙酯（IS）会加速肾脏损伤和心血管疾病的恶化。硫酸吲哚乙酯可能会诱发内皮细胞炎症，从而导致血管疾病。叶黄素具有抗氧化和抗炎特性。本研究旨在探讨叶黄素对 IS 介导的活性氧（ROS）产生、EA.hy926 细胞中细胞间粘附分子（ICAM-1）和单核细胞趋化蛋白（MCP-1）表达的影响及其可能的机制。IS 能明显诱导 ROS 的产生（6.03 倍，p

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来源期刊

Environmental Toxicology 环境科学-毒理学

CiteScore

7.10

自引率

8.90%

发文量

261

审稿时长

4.5 months

期刊介绍： The journal publishes in the areas of toxicity and toxicology of environmental pollutants in air, dust, sediment, soil and water, and natural toxins in the environment.Of particular interest are: Toxic or biologically disruptive impacts of anthropogenic chemicals such as pharmaceuticals, industrial organics, agricultural chemicals, and by-products such as chlorinated compounds from water disinfection and waste incineration; Natural toxins and their impacts; Biotransformation and metabolism of toxigenic compounds, food chains for toxin accumulation or biodegradation; Assays of toxicity, endocrine disruption, mutagenicity, carcinogenicity, ecosystem impact and health hazard; Environmental and public health risk assessment, environmental guidelines, environmental policy for toxicants.