title: Effects of PCB126 and 17β-oestradiol on endothelium-derived vasoactive factors in human endothelial cells.
abstract: Epidemiological and experimental studies suggest an association between elevated serum levels of co-planar PCBs and hypertension, and one study indicate that this effect is dependent on the level of oestrogen. This study investigated the effects of 3,3',4,4',5-pentachlorobiphenyl (PCB126) and 17β-oestradiol (E₂) on vasoactive factors in human umbilical vein endothelial cells (HUVEC). The results reveal that PCB126 stimulated the vasoconstriction factors COX-2 and PGF(2α) in HUVEC. An up-regulation of COX-2 expression was demonstrated using qRT-PCR, western blot and immunofluorescence and increased production of PGF(2α) was demonstrated using LC/MS² and enzyme immunoassay. Also, PCB126 slightly increased ROS production and decreased NO production in HUVEC. The addition of E₂ enhanced PCB126-induced transcription of CYP1A1, CYP1B1 and COX-2 in HUVEC whereas an increased transcription of eNOS only occurred following combined treatment with E₂ and PCB126. Immunofluorescence demonstrated that HUVEC expressed AHR and ERβ but lacked ERα and the involvement of AHR and ERβ on the effects of PCB126 was examined by the addition of AHR and ER antagonists. The binding of PCB126 to AHR was critical for the effects of PCB126 whereas the role of ERβ was equivocal. In conclusion, these studies suggest that PCB126 induced changes in human endothelial cells that are characteristic for endothelial dysfunction in human hypertension and that PCB126-induced transcription of genes important for vascular function in human endothelial cells can be elevated by increased oestrogen levels. These findings may help understanding the mechanism for the association between PCB126 exposure and hypertension reported in human subjects and experimental animals.
authors.affiliation: Uppsala University, Department of Pharmaceutical Biosciences, Box 591, SE-75124 Uppsala, Sweden. Helen.andersson@farmbio.uu.se
authors.forename: Helén
authors.initials: H
authors.lastname: Andersson
authors.forename: Ulrike
authors.initials: U
authors.lastname: Garscha
authors.forename: Eva
authors.initials: E
authors.lastname: Brittebo
mesh_terms: D002478:Cells, Cultured; D051546:Cyclooxygenase 2 / Q000187:drug effects / Q000235:genetics / Q000378:metabolism; D015237:Dinoprost / Q000378:metabolism; D042783:Endothelial Cells / Q000187:drug effects* / Q000378:metabolism; D004730:Endothelium, Vascular / Q000187:drug effects / Q000378:metabolism; D004958:Estradiol / Q000494:pharmacology*; D004965:Estrogen Antagonists / Q000633:toxicity*; D005455:Fluorescent Antibody Technique; D006801:Humans; D009569:Nitric Oxide / Q000096:biosynthesis; D011078:Polychlorinated Biphenyls / Q000633:toxicity*; D011485:Protein Binding; D017382:Reactive Oxygen Species / Q000378:metabolism; D018336:Receptors, Aryl Hydrocarbon / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014158:Transcription, Genetic / Q000187:drug effects; D014471:Umbilical Veins / Q000166:cytology; D015854:Up-Regulation / Q000187:drug effects
chemical_list: D004965:Estrogen Antagonists; D017382:Reactive Oxygen Species; D018336:Receptors, Aryl Hydrocarbon; D009569:Nitric Oxide; D004958:Estradiol; D015237:Dinoprost; D011078:Polychlorinated Biphenyls; D051546:Cyclooxygenase 2; C023035:3,4,5,3',4'-pentachlorobiphenyl