Brominated flame retardants, hexabromocyclododecane and tetrabromobisphenol A, affect proinflammatory protein expression in human bronchial epithelial cells via disruption of intracellular signaling. (April 2016)

• Record Type: Journal Article
• Authors: Koike, Eiko; Yanagisawa, Rie; Takano, Hirohisa
• Is Part Of: Toxicology in vitro. Volume 32(2016)
• Page Start: 212
• Page End: 219
• Publication Date: 2016-04
• Subjects: AhR aryl hydrocarbon receptor -- AP-1 activator protein 1 -- BFRs brominated flame retardants -- DMSO dimethyl sulfoxide -- EGF epidermal growth factor -- EGFR EGF receptor -- ELISA enzyme linked immunosorbent assay -- ER estrogen receptor -- HBCD hexabromocyclododecane -- ICAM intercellular adhesion molecule -- IL interleukin -- MAPK mitogen-activated protein kinase -- NFκB nuclear factor-kappa B -- PBDEs polybrominated diphenyl ethers -- STAT signal transducer and activator of transcription -- TBBPA tetrabromobisphenol A -- TR thyroid hormone receptor; Hexabromocyclododecane -- Tetrabromobisphenol a -- Bronchial epithelial cells -- Proinflammatory proteins -- Epidermal growth factor receptor -- Nuclear receptor; Toxicity testing -- In vitro -- Periodicals; Toxicology -- Periodicals; 615.9
• DOI: 10.1016/j.tiv.2015.12.013
• Languages: English
• ISSNs: 0887-2333

Abstract

Abstract: Hexabromocyclododecane (HBCD) and tetrabromobisphenol A (TBBPA) are widely used as brominated flame retardants (BFRs) in consumer products. Because humans can be exposed to BFRs mainly through air or dust, the effects of the BFRs on the respiratory system and the underlying mechanisms were investigated. HBCD exposure significantly increased the expression of intercellular adhesion molecule (ICAM)-1 and the production of interleukin (IL)-6 and -8 in human bronchial epithelial cells (BEAS-2B). TBBPA exposure significantly increased the expression of ICAM-1 and IL-6, but not IL-8. HBCD and TBBPA stimulated epidermal growth factor (EGF) production and EGF receptor (EGFR) phosphorylation. Inhibitors of EGFR-selective tyrosine kinase and the subsequent mitogen-activated protein kinase effectively blocked the increase in the expression of proinflammatory proteins. The activation of nuclear factor-kappa B (p50, p65) and activator protein 1 (c-Jun) was also observed following HBCD exposure. Furthermore, the modulation for nuclear receptors was investigated. TBBPA but not HBCD showed ligand activity for thyroid hormone receptor (TR) and TR antagonist significantly suppressed the TBBPA-induced increase of the expression of ICAM-1 and IL-6. In conclusion, HBCD and TBBPA can disrupt the expression of proinflammatory proteins in bronchial epithelial cells, possibly via the modulation of EGFR-related pathways and/or nuclear receptors. Highlights: HBCD and TBBPA affect the viability and proliferation in BEAS-2B cells. HBCD and TBBPA affect the expression of proinflammatory proteins in BEAS-2B cells. HBCD and TBBPA stimulate EGFR-related protein phosphorylation. TBBPA may affect inflammatory response via disrupt nuclear receptor signaling pathways.