Gdula-Argasińska Joanna, Czepiel Jacek, Totoń-Żurańska Justyna, Jurczyszyn Artur, Perucki William, Wołkow Paweł
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.
Toxicol Lett. 2015 Jul 16;236(2):75-81. doi: 10.1016/j.toxlet.2015.05.002. Epub 2015 May 5.
The molecular mechanism of inflammation and carcinogenesis induced by exposure of polycyclic aromatic hydrocarbons (PAHs) is not clearly understood. Our study was undertaken due to the strong pro-carcinogenic potential and reactivity of PAH-metabolites, as well as the susceptibility of polyunsaturated fatty acids to oxidation. The aim of this study was to evaluate the pro- or anti-inflammatory impact of n-3 docosahexaenoic acid on human primary umbilical vein endothelial cells (HUVEC) exposed to polycyclic aromatic hydrocarbons. We analysed the influence of docosahexaenoic acid (DHA) and/or PAHs supplementation on the fatty acid profile of cell membranes, on cyclooxygenase-2 (COX-2), aryl hydrocarbon receptor (AHR), and glutathione S transferase Mu1 (GSTM1) protein expression as well as on the prostaglandin synthase 2 (PTGS2), AHR, GSTM1, PLA2G4A, and cytochrome P450 CYP1A1 gene expression. We observed that COX-2 and AHR protein expression was increased while GSTM1 expression was decreased in cells exposed to DHA and PAHs. Docosahexaenoic acid down-regulated CYP1A1 and up-regulated the AHR and PTGS2 genes. Our findings suggested that DHA contributes significantly to alleviate the harmful effects caused by PAHs in endothelial cells. Moreover, these results suggest that a diet rich in n-3 fatty acids is helpful to reduce the harmful effects of PAHs exposure on human living in heavily polluted areas.
多环芳烃（PAHs）暴露所引发的炎症和致癌作用的分子机制尚未完全明晰。我们开展这项研究是鉴于PAH代谢产物具有强大的促癌潜力和反应活性，以及多不饱和脂肪酸易于氧化的特性。本研究的目的是评估n-3二十二碳六烯酸对暴露于多环芳烃的人脐静脉内皮细胞（HUVEC）的促炎或抗炎影响。我们分析了二十二碳六烯酸（DHA）和/或PAHs补充剂对细胞膜脂肪酸谱、环氧合酶-2（COX-2）、芳烃受体（AHR）和谷胱甘肽S-转移酶Mu1（GSTM1）蛋白表达的影响，以及对前列腺素合酶2（PTGS2）、AHR、GSTM1、磷脂酶A2G4A和细胞色素P450 CYP1A1基因表达的影响。我们观察到，在暴露于DHA和PAHs的细胞中，COX-2和AHR蛋白表达增加，而GSTM1表达降低。二十二碳六烯酸下调CYP1A1并上调AHR和PTGS2基因。我们的研究结果表明，DHA对减轻PAHs在内皮细胞中造成的有害影响有显著作用。此外，这些结果表明，富含n-3脂肪酸的饮食有助于减少PAHs暴露对生活在重度污染地区人群的有害影响。
