Delineation of 3D dose-time-toxicity in human pulmonary epithelial Beas-2B cells induced by decabromodiphenyl ether (BDE209)

Environ Pollut. 2018 Dec;243(Pt A):661-669. doi: 10.1016/j.envpol.2018.09.047. Epub 2018 Sep 11.

Abstract

Due to frequent detection in environment as well as in the human body, the adverse effects of decabromodiphenyl ether (BDE209) have been extensively studied in the past few years. However, information regarding the inhalation toxicity of BDE209 to humans is currently limited. In this study, the cytotoxicity, cell damage, and inflammation markers including IL-6, IL-8, and TNF-α in the Beas-2B cell line induced by BDE209 were measured using a central composite design. Results showed that as BDE209 concentrations (5-65 μg mL-1) and exposure time (6-30 h) were increased, cell viability sharply decreased from 99.7% to 29.7% and LDH activity increased from 0.1% to 13.1%. Furthermore, expression of IL-6, IL-8 and TNF-α transcripts were enhanced from 4.7 to 29.1 fold, 3.4-68.9 fold, and 2.8-47.0 fold, respectively, and the concentration of IL-6 and IL-8 proteins increased from 5.4 to 16.7 pg mL-1 and 71.0-550.0 pg mL-1, respectively. Results indicate that BDE209 exposure can inhibit cell viability, increase LDH leakage, and upregulate the transcript (mRNA) and protein levels of inflammatory markers of IL-6 and IL-8 in Beas-2B cells. Moreover, these effects were both dose- and time-dependent, and dose and time had a synergistic effect - enhancing toxicity when in combination. Cell density affected both LDH activity and IL-8 release but had little effect on cell activity and IL-6 release in the Beas-2B cells. In contrast, TNF-α protein was not detected but its mRNA expression level was upregulated. This study will provide a reference for human health risk assessment, especially for the toxic damage that BDE209 exposure can elicit in the respiratory tract.

Keywords: BDE209; Beas-2B cell; Cell damage; Cytotoxicity; Inflammatory cytokines.

MeSH terms

  • Air Pollutants / toxicity
  • Bronchi / drug effects*
  • Cell Line
  • Cell Survival / drug effects
  • Epithelial Cells / drug effects*
  • Gene Expression / drug effects*
  • Halogenated Diphenyl Ethers / toxicity*
  • Humans
  • Inflammation / metabolism
  • Interleukin-6 / metabolism
  • Interleukin-8 / metabolism
  • RNA, Messenger / biosynthesis*
  • Transcription, Genetic / drug effects
  • Tumor Necrosis Factor-alpha / metabolism

Substances

  • Air Pollutants
  • CXCL8 protein, human
  • Halogenated Diphenyl Ethers
  • IL6 protein, human
  • Interleukin-6
  • Interleukin-8
  • RNA, Messenger
  • Tumor Necrosis Factor-alpha
  • decabromobiphenyl ether