title: Bisphenol A exposure alters release of immune and developmental modulators and expression of estrogen receptors in human fetal lung fibroblasts.
abstract: 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 24hr. Effects of BPA on localization and uptake of BPA, cell viability, release of immune and developmental modulators, cellular localization and expression of ERα, 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 0.01-100μmol/L caused no changes in cell viability after 24hr of exposure. hFLFs expresses all three ERs. BPA had no effects on either cellular distribution or protein expression of ERα, however, at 100μmol/L (or 23μmol/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 100μmol/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 vivo studies.
authors.affiliation: Regulatory Toxicology Research Division, Bureau of Chemical Safety, Food Directorate, HPFB, Health Canada, Ottawa, Ontario, Canada; Institute of Biochemistry, Departments of Biology and Chemistry, Carleton University, Ottawa, Ontario, Canada. Electronic address: Mahemuti_Laziyan@hc-sc.gc.ca.
authors.forename: Laziyan
authors.initials: L
authors.lastname: Mahemuti
authors.affiliation: Regulatory Toxicology Research Division, Bureau of Chemical Safety, Food Directorate, HPFB, Health Canada, Ottawa, Ontario, Canada.
authors.forename: Qixuan
authors.initials: Q
authors.lastname: Chen
authors.affiliation: Regulatory Toxicology Research Division, Bureau of Chemical Safety, Food Directorate, HPFB, Health Canada, Ottawa, Ontario, Canada.
authors.forename: Melanie C
authors.initials: MC
authors.lastname: Coughlan
authors.affiliation: Regulatory Toxicology Research Division, Bureau of Chemical Safety, Food Directorate, HPFB, Health Canada, Ottawa, Ontario, Canada.
authors.forename: Min
authors.initials: M
authors.lastname: Zhang
authors.affiliation: Regulatory Toxicology Research Division, Bureau of Chemical Safety, Food Directorate, HPFB, Health Canada, Ottawa, Ontario, Canada; Institute of Biochemistry, Departments of Biology and Chemistry, Carleton University, Ottawa, Ontario, Canada.
authors.forename: Maria
authors.initials: M
authors.lastname: Florian
authors.affiliation: Regulatory Toxicology Research Division, Bureau of Chemical Safety, Food Directorate, HPFB, Health Canada, Ottawa, Ontario, Canada; Institute of Biochemistry, Departments of Biology and Chemistry, Carleton University, Ottawa, Ontario, Canada.
authors.forename: Ryan J
authors.initials: RJ
authors.lastname: Mailloux
authors.affiliation: Food Research Division, Bureau of Chemical Safety, Food Directorate, HPFB, Health Canada, Ontario, Canada.
authors.forename: Xu-Liang
authors.initials: XL
authors.lastname: Cao
authors.affiliation: Nutrition Research Division, Bureau of Nutritional Sciences, Food Directorate, HPFB, Health Canada, Ottawa, Ontario, Canada; Sector Strategies Division, Risk Management Bureau, Safe Environments Directorate, HECSB, Health Canada, Ottawa, Ontario, Canada.
authors.forename: Kylie A
authors.initials: KA
authors.lastname: Scoggan
authors.affiliation: Institute of Biochemistry, Departments of Biology and Chemistry, Carleton University, Ottawa, Ontario, Canada.
authors.forename: William G
authors.initials: WG
authors.lastname: Willmore
authors.affiliation: Regulatory Toxicology Research Division, Bureau of Chemical Safety, Food Directorate, HPFB, Health Canada, Ottawa, Ontario, Canada. Electronic address: Dawn_Jin@hc-sc.gc.ca.
authors.forename: Xiaolei
authors.initials: X
authors.lastname: Jin
mesh_terms: D001559:Benzhydryl Compounds / Q000633:toxicity*; D002460:Cell Line; D052244:Endocrine Disruptors / Q000633:toxicity; D004968:Estrogens, Non-Steroidal / Q000633:toxicity*; D005347:Fibroblasts; D006801:Humans; D015850:Interleukin-6 / Q000378:metabolism; D010636:Phenols / Q000633:toxicity*; D011960:Receptors, Estrogen / Q000378:metabolism; D000098826:Bisphenol A Compounds
chemical_list: D001559:Benzhydryl Compounds; D052244:Endocrine Disruptors; D004968:Estrogens, Non-Steroidal; D015850:Interleukin-6; D010636:Phenols; D011960:Receptors, Estrogen; C006780:bisphenol A; D000098826:Bisphenol A Compounds
keywords: Antagonists; Bisphenol A; Chemokines; Cytokines; Estrogen receptors; Human fetal lung fibroblasts; Immune and developmental modulators