title: Penta- and octa-bromodiphenyl ethers promote proinflammatory protein expression in human bronchial epithelial cells in vitro.
abstract: Polybrominated diphenyl ethers (PBDEs) are widely used as flame retardants in consumer products. Humans can be exposed to PBDEs mainly through the inhalation of air or dust. Thus, PBDEs can affect respiratory and immune systems. In the present study, we investigated whether PBDEs stimulate bronchial epithelial cells. We examined commercial penta-BDE (DE-71), octa-BDE (DE-79), and deca-BDE (DE-83R). Human bronchial epithelial cells (BEAS-2B) were exposed to each PBDE for 24h. Subsequently, the expression of intercellular adhesion molecule-1 (ICAM-1) and proinflammatory cytokines were investigated. DE-71 and DE-79, but not DE-83R, significantly increased the expression of ICAM-1, interleukin-6 (IL-6), and IL-8 in BEAS-2B. Because these remarkable effects were observed with DE-71, we further investigated the underlying intracellular mechanisms. DE-71 promoted epidermal growth factor receptor (EGFR) phosphorylation. Inhibitors of EGFR-selective tyrosine kinase and p38 mitogen-activated protein kinase effectively blocked the increase of IL-6 and IL-8. Furthermore, antagonists of thyroid hormone receptor and aryl hydrocarbon receptor significantly suppressed the increase in IL-6 and/or IL-8 production. In conclusion, penta- and octa-BDE, but not deca-BDE, might promote the expression of proinflammatory proteins in bronchial epithelial cells possibly by activating protein kinases and/or stimulating nuclear receptors related to subsequent activation of transcriptional factors.
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: Center for Material Cycles and Waste Management Research, National Institute for Environmental Studies, 16-2 Onogawa, Tsukuba, Ibaraki 305-8506, Japan.
authors.forename: Hidetaka
authors.initials: H
authors.lastname: Takigami
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 / Q000187:drug effects / Q000378:metabolism*; D002460:Cell Line; D049109:Cell Proliferation / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D003470:Culture Media; D004847:Epithelial Cells / Q000187:drug effects / Q000378:metabolism*; D066246:ErbB Receptors / Q000096:biosynthesis; D005411:Flame Retardants / Q000633:toxicity*; D005434:Flow Cytometry; D055768:Halogenated Diphenyl Ethers / Q000633:toxicity*; D006801:Humans; D007249:Inflammation / Q000378:metabolism; D018799:Intercellular Adhesion Molecule-1 / Q000096:biosynthesis; D015850:Interleukin-6 / Q000096:biosynthesis; D016209:Interleukin-8 / Q000096:biosynthesis; D010766:Phosphorylation; D020545:Respiratory Mucosa / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D015398:Signal Transduction / Q000187:drug effects
chemical_list: D003470:Culture Media; D005411:Flame Retardants; D055768:Halogenated Diphenyl Ethers; D015850:Interleukin-6; D016209:Interleukin-8; D018799:Intercellular Adhesion Molecule-1; C086401:pentabromodiphenyl ether; D066246:ErbB Receptors
keywords: AhR; BFRs; Brominated flame retardants; Bronchial epithelial cells; DMSO; EGF; EGF receptor; EGFR; ELISA; ER; Epidermal growth factor receptor; HBCD; ICAM; IL; MAPK; PBDEs; Polybrominated diphenyl ethers; Proinflammatory cytokines; STAT; TR; aryl hydrocarbon receptor; brominated flame retardants; dimethyl sulfoxide; enzyme linked immunosorbent assay; epidermal growth factor; estrogen receptor; hexabromocyclododecane; intercellular adhesion molecule; interleukin; mitogen-activated protein kinase; polybrominated diphenyl ethers; signal transducer and activator of transcription; thyroid hormone receptor