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在经苯并(a)芘处理的人脐静脉内皮细胞(HUVEC)中,消退素D1下调细胞色素P450 1A1(CYP1A1)和环氧化酶-2(PTGS2)基因。

Resolvin D1 down-regulates CYP1A1 and PTGS2 gene in the HUVEC cells treated with benzo(a)pyrene.

作者信息

Gdula-Argasińska Joanna, Czepiel Jacek, Totoń-Żurańska Justyna, Jurczyszyn Artur, Wołkow Paweł, Librowski Tadeusz, Perucki William

机构信息

Department of Radioligands, Faculty of Pharmacy, Jagiellonian University, Medical College, Kraków, Poland.

Department of Infectious Diseases, Faculty of Medicine, Jagiellonian University Medical College, Kraków, Poland.

出版信息

Pharmacol Rep. 2016 Oct;68(5):939-44. doi: 10.1016/j.pharep.2016.05.005. Epub 2016 Jun 27.

Abstract

BACKGROUND

Polycyclic aromatic hydrocarbons (PAHs) can interact with lipids and their derivatives and have been known to induce atherosclerosis. The aim of this study was to evaluate the impact of Resolvin D1 (RvD1) on inflammatory-state realted proteins and genes in the human primary umbilical vein endothelial HUVEC cells exposed to benzo(a)pyrene (BaP).

METHODS

We analyzed the influence of RvD1 and/or BaP on cyclooxygenase-2 (COX-2), cytosolic prostaglandine E2 synthase (cPGES), glutathione S transferase (GSTM1) and aryl hydrocarbon receptor (AhR) protein expression by Western blot. Additionaly, phospholipase A2 (cPLA2) and cytochrome P450 (CYP1A1) activity, as well as AhR, CYP1A1, phospholipase A2 (PLA2G4A) and prostaglandin synthase 2 (PTGS2) gene expression by qRT-PCR was studied.

RESULTS

RvD1 down-regulates cytochrome P450 (CYP1A1) and prostaglandin synthase 2 (PTGS2) gene expression in HUVEC cells exposed to BaP. Repressesion of COX-2, cPGES and overexpressesion of GSTM1 protein was noted after co-treatment with RvD1 and BaP. After incubation with RvD1 an increase of cPLA2 and a decrease of CYP1A1 activity was observed when compared to BaP treated alone endothelial cells.

CONCLUSIONS

Our data suggests that RvD1 can significantly contributes on vascular function and alleviates the harmful effects caused by BaP, which might potentially aid in the repair of the injured endothelium.

摘要

背景

多环芳烃(PAHs)可与脂质及其衍生物相互作用,已知会诱发动脉粥样硬化。本研究的目的是评估消退素D1(RvD1)对暴露于苯并(a)芘(BaP)的人原代脐静脉内皮HUVEC细胞中炎症相关蛋白和基因的影响。

方法

我们通过蛋白质印迹法分析了RvD1和/或BaP对环氧合酶-2(COX-2)、胞质前列腺素E2合酶(cPGES)、谷胱甘肽S转移酶(GSTM1)和芳烃受体(AhR)蛋白表达的影响。此外,通过qRT-PCR研究了磷脂酶A2(cPLA2)和细胞色素P450(CYP1A1)的活性,以及AhR、CYP1A1、磷脂酶A2(PLA2G4A)和前列腺素合酶2(PTGS2)的基因表达。

结果

RvD1下调了暴露于BaP的HUVEC细胞中细胞色素P450(CYP1A1)和前列腺素合酶2(PTGS2)的基因表达。与RvD1和BaP共同处理后,观察到COX-2、cPGES的抑制以及GSTM1蛋白的过表达。与单独用BaP处理的内皮细胞相比,用RvD1孵育后,观察到cPLA2增加,CYP1A1活性降低。

结论

我们的数据表明,RvD1可显著促进血管功能,减轻BaP造成的有害影响,这可能有助于修复受损的内皮。

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