Diamond Michael P, Wirth Julie J, Saed Ghassan M
Division of Reproductive Endocrinology and Infertility, Department of Obstetrics and Gynecology, Wayne State University, Detroit, Michigan 48201, USA.
Fertil Steril. 2008 Oct;90(4 Suppl):1372-5. doi: 10.1016/j.fertnstert.2007.07.1380. Epub 2007 Sep 20.
To test the effect of four polychlorinated biphenyl congeners (PCB-77, PCB-105, PCB 153, and PCB 180) on expression of three adhesion markers (transforming growth factor [TGF] beta1, vascular endothelial growth factor [VEGF], and type I collagen) in normal human peritoneal and adhesion fibroblasts.
Cell culture study.
University research laboratory.
PATIENT(S): Primary cultures of normal peritoneal and adhesion fibroblasts were established from three patients.
INTERVENTION(S): Fibroblasts were treated with PCB-77, PCB-105, PCB-153, or PCB-180 at 20 ppm for 24 hours. Total RNA was extracted from each treatment and subjected to real-time reverse transcriptase polymerase chain reaction (RT-PCR). MAIN OUTCOME AND MEASURE(S): The mRNA levels of type I collagen, VEGF, and TGF-beta1.
RESULT(S): Normal human peritoneal fibroblasts expressed type I collagen, VEGF, and TGF-beta1. Exposure of normal human fibroblasts to PCB-77, PCB-105, PCB-153, or PCB-180 did not affect mRNA levels of beta-actin, the housekeeping gene used to normalized RNA levels for the real-time RT-PCR, nor did it affect cell viability as assessed by trypan blue exclusion. The PCB treatments, compared with control, resulted in no significant change for TGF-beta1 or VEGF mRNA levels in normal peritoneal and adhesion fibroblasts. In marked contrast, type I collagen mRNA levels were markedly increased in response to the brief 24 hours' exposure to each PCB treatment in both cell types.
CONCLUSION(S): The finding that PCB-77, PCB-105, PCB-153, and PCB-180 increased the expression of type I collagen in human normal peritoneal and adhesion fibroblasts is the first demonstration of involvement of organochlorines in the pathogenesis of tissue fibrosis. This may implicate organochlorine exposure as an etiologic factor in a wide variety of previously unlinked human ailments characterized by fibrosis.
检测四种多氯联苯同系物(PCB - 77、PCB - 105、PCB 153和PCB 180)对正常人腹膜成纤维细胞和粘连成纤维细胞中三种黏附标志物(转化生长因子[TGF]β1、血管内皮生长因子[VEGF]和I型胶原蛋白)表达的影响。
细胞培养研究。
大学研究实验室。
从三名患者中建立正常人腹膜成纤维细胞和粘连成纤维细胞的原代培养物。
将成纤维细胞用浓度为20 ppm的PCB - 77、PCB - 105、PCB - 153或PCB - 180处理24小时。从每种处理中提取总RNA,并进行实时逆转录聚合酶链反应(RT - PCR)。
I型胶原蛋白、VEGF和TGF - β1的mRNA水平。
正常人腹膜成纤维细胞表达I型胶原蛋白、VEGF和TGF - β1。正常人成纤维细胞暴露于PCB - 77、PCB - 105、PCB - 153或PCB - 180后,看家基因β - 肌动蛋白的mRNA水平不受影响,β - 肌动蛋白用于实时RT - PCR中RNA水平的标准化,锥虫蓝排斥法评估细胞活力也未受影响。与对照组相比,PCB处理对正常人腹膜成纤维细胞和粘连成纤维细胞中TGF - β1或VEGF的mRNA水平无显著影响。与之形成鲜明对比的是,两种细胞类型在短暂暴露于每种PCB处理24小时后,I型胶原蛋白的mRNA水平均显著升高。
PCB - 77、PCB - 105、PCB - 153和PCB - 180增加人正常腹膜成纤维细胞和粘连成纤维细胞中I型胶原蛋白表达的这一发现,首次证明了有机氯参与组织纤维化的发病机制。这可能意味着有机氯暴露是多种以前未关联的以纤维化为特征的人类疾病的病因。