Bisphenol A exposure alters release of immune and developmental modulators and expression of estrogen receptors in human fetal lung fibroblasts

作     者：Laziyan Mahemuti Qixuan Chen Melanie C. Coughlan Min Zhang Maria Florian Ryan J Mailloux Xu-Liang Cao Kylie A. Scoggan William G. Willmore Xiaolei Jin 

作者机构：Regulatory Toxicology Research Division Bureau of Chemical Safety Food Directorate HPFB Health Canada Ottawa Ontario Canada Food Research Division Bureau of Chemical Safety Food Directorate HPFB Health Canada Ontario Canada Nutrition Research Division Bureau of Nutritional Sciences Food Directorate HPFB Heakh Canada Ottawa Ontario Canada Sector Strategies Division Risk Management Bureau Safe Environments Directorate HECSB Health Canada Ottawa Ontario Canada Institute of Biochemistry Departments of Biology and Chemistry Carleton University Ottawa Ontario Canada 

出 版 物：《Journal of Environmental Sciences》 (环境科学学报（英文版）)

年 卷 期：2016年第28卷第10期

页      面：11-23页

核心收录：

学科分类：0830[工学-环境科学与工程（可授工学、理学、农学学位）] 1002[医学-临床医学] 100211[医学-妇产科学] 10[医学] 

基　　金：supported by a grant from the Chemical Management Plan an initiative of the Government of Canada aimed at reducing the risks posed by chemicals to Canadians and their environment the Regulatory Toxicology Research Division, Bureau of Chemical Safety, Food Directorate, Health Canada to XJ a Discovery Grant from the Natural Sciences and Engineering Research Council (NSERC) of Canada to WGW 

主　　题：Bisphenol AHuman fetal lung fibroblastsEstrogen receptorsAntagonistsCytokinesChemokinesImmune and developmentalmodulators 

摘      要：Bisphenol A （BPA） has been shown to exert biological effects through estrogen receptor （ER）-dependent and ER-independent mechanisms. Recent studies suggest that prenatal exposure to BPA may increase the risk of childhood asthma. To investigate the underlying mechanisms in the actions of BPA, human fetal lung fibroblasts {hFLFs） were exposed to varying doses of BPA in culture for 24 hr. Effects of BPA on localization and uptake of BPA, cell viability, release of immune and developmental modulators, cellular localization and expression of ERa, ERβ and G-protein coupled estrogen receptor 30 （GPR30）, and effects of ERs antagonists on BPA-induced changes in endothelin-1 （ET-1） release were examined. BPA at 0.01-100 μmol/L caused no changes in cell viability after 24 hr of exposure, hFLFs expresses all three ERs. BPA had no effects on either cellular distribution or protein expression of ERa, however, at 100 μmol/L （or 23 μmol/L intracellular BPA） increased ERβ protein levels in the cytoplasmic fractions and GPR30 protein levels in the nuclear fractions. These paralleled with increased release of growth differentiation factor-15, decreased phosphorylation of nuclear factor kappa B p65 at serine 536, and decreased release of ET-1, interleukin-6, and interferon gamma-induced protein 10. ERs antagonists had no effects on BPA-induced decrease in ET-1 release. These data suggest that BPA at 100 μmol/L altered the release of immune and developmental modulators in hFLFs, which may negatively influence fetal lung development, maturation, and susceptibility to environmental stressors, although the role of BPA in childhood asthma remains to be confirmed in in viuo studies.