title: Brominated flame retardants, hexabromocyclododecane and tetrabromobisphenol A, affect proinflammatory protein expression in human bronchial epithelial cells via disruption of intracellular signaling.
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.
authors.affiliation: Center for Environmental Health Sciences, National Institute for Environmental Studies, 16-2 Onogawa, Tsukuba, Ibaraki 305-8506, Japan. Electronic address: ekoike@nies.go.jp.
authors.forename: Eiko
authors.initials: E
authors.lastname: Koike
authors.affiliation: Center for Environmental Health Sciences, National Institute for Environmental Studies, 16-2 Onogawa, Tsukuba, Ibaraki 305-8506, Japan.
authors.forename: Rie
authors.initials: R
authors.lastname: Yanagisawa
authors.affiliation: Graduate School of Engineering, Kyoto University, Kyoto daigaku-Katsura, Nishikyo-ku, Kyoto 615-8530, Japan.
authors.forename: Hirohisa
authors.initials: H
authors.lastname: Takano
mesh_terms: D001980:Bronchi / Q000166:cytology; D002460:Cell Line; D002470:Cell Survival / Q000187:drug effects; D004815:Epidermal Growth Factor / Q000378:metabolism; D004847:Epithelial Cells / Q000187:drug effects* / Q000378:metabolism; D066246:ErbB Receptors / Q000378:metabolism; D005411:Flame Retardants / Q000633:toxicity*; D006801:Humans; D006842:Hydrocarbons, Brominated / Q000633:toxicity*; D018799:Intercellular Adhesion Molecule-1 / Q000378:metabolism; D015850:Interleukin-6 / Q000378:metabolism; D016328:NF-kappa B / Q000378:metabolism; D011075:Polybrominated Biphenyls / Q000633:toxicity*; D011987:Receptors, Steroid / Q000378:metabolism; D050796:STAT3 Transcription Factor / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects; D018808:Transcription Factor AP-1 / Q000378:metabolism
chemical_list: D005411:Flame Retardants; D006842:Hydrocarbons, Brominated; C573420:ICAM1 protein, human; C508600:IL6 protein, human; D015850:Interleukin-6; D016328:NF-kappa B; D011075:Polybrominated Biphenyls; D011987:Receptors, Steroid; D050796:STAT3 Transcription Factor; C494086:STAT3 protein, human; D018808:Transcription Factor AP-1; D018799:Intercellular Adhesion Molecule-1; C089796:hexabromocyclododecane; D004815:Epidermal Growth Factor; C512478:EGFR protein, human; D066246:ErbB Receptors; C020806:tetrabromobisphenol A
keywords: Bronchial epithelial cells; Epidermal growth factor receptor; Hexabromocyclododecane; Nuclear receptor; Proinflammatory proteins; Tetrabromobisphenol a