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

详细信息    查看全文

• 作者：Laziyan Mahemuti¹ ; ⁵ ; ^{Mahemuti_Laziyan@hc-sc.gc.ca" class="auth_mail" title="E-mail the corresponding author} ; Qixuan Chen¹ ; Melanie C. Coughlan¹ ; Min Zhang¹ ; Maria Florian¹ ; ⁵ ; Ryan J. Mailloux¹ ; ⁵ ; Xu-Liang Cao² ; Kylie A. Scoggan³ ; ⁴ ; William G. Willmore⁵ ; Xiaolei Jin¹ ; ^{Dawn_Jin@hc-sc.gc.ca" class="auth_mail" title="E-mail the corresponding author} ; ^{jxnc329@gmail.com" class="auth_mail" title="E-mail the corresponding author}
• 关键词：Bisphenol A ; Human fetal lung fibroblasts ; Estrogen receptors ; Antagonists ; Cytokines ; Chemokines ; Immune and developmental modulators
• 刊名：Journal of Environmental Sciences
• 出版年：2016
• 出版时间：October 2016
• 年：2016
• 卷：48
• 期：Complete
• 页码：11-23
• 全文大小：1221 K

文摘

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 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 0.01–100 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 ERα, 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 vivo studies.