Health & Environmental Research Online (HERO)


Print Feedback Export to File
3350501 
Journal Article 
Brominated flame retardants, hexabromocyclododecane and tetrabromobisphenol A, affect proinflammatory protein expression in human bronchial epithelial cells via disruption of intracellular signaling 
Koike, E; Yanagisawa, R; Takano, H 
2016 
1 
Toxicology In Vitro
ISSN: 0887-2333
EISSN: 1879-3177 
32 
212-219 
English 
26718265 
WOS:000372760900024 
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. 
Hexabromocyclododecane; Tetrabromobisphenol a; Bronchial epithelial cells; Proinflammatory proteins; Epidermal growth factor receptor; Nuclear receptor 
IRIS
• Hexabromocyclododecane (HBCD)
     New 7/2016 (private)
     Database Searches
          Pubmed
          WOS
     Sources of Mechanistic and Toxicokinetic Data
          Mechanistic and genotoxicity studies
OPPT REs
• OPPT_Cyclic Aliphatic Bromine Cluster (HBCD)_F. Human Health
     Total – title/abstract screening
          On topic
               Peer review
                    Primary source
               Cited in IRIS document or IRIS HERO page
     On topic - additional tags for titles/abstracts
          MOA