The flame retardants tetrabromobisphenol A and tetrabromobisphenol A–bisallylether suppress the induction of interleukin-2 receptor α chain (CD25) in murine splenocytes

Polybrominated flame retardants (PBF) are frequently used additives in electronical equipment. They are ubiquitous environmental contaminants which bioaccumulate with several health effects for humans and the environment. This study investigated immunotoxic effects of the PBF tetrabromobisphenol A (...

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Published in:	Toxicology (Amsterdam) Vol. 184; no. 1; pp. 11 - 22
Main Authors:	Pullen, Sabine, Boecker, Ronald, Tiegs, Gisa
Format:	Journal Article
Language:	English
Published:	Shannon Elsevier Ireland Ltd 14-02-2003 Amsterdam Elsevier Science
Subjects:	Ah-receptor Animals Biological and medical sciences Cell Separation Cell Survival - drug effects Chemical and industrial products toxicology. Toxic occupational diseases Cytochrome P-450 CYP1A1 - biosynthesis Cytochrome P450 1A1 Cytokines - metabolism Enzyme Induction - drug effects Enzyme-Linked Immunosorbent Assay Female Flame Retardants - toxicity Hepatocytes - drug effects IL-2 receptor α chain (CD25) Immunohistochemistry Immunotoxicity Indicators and Reagents Interleukin-2 - biosynthesis Laser scanning cytometry Medical sciences Mice Mice, Inbred C57BL Microscopy, Confocal Polybrominated Biphenyls - toxicity Polybrominated flame retardants Receptors, Interleukin-2 - biosynthesis Solutions Spleen - cytology Spleen - drug effects Spleen - metabolism Tetrazolium Salts Thiazoles Toxicology Various organic compounds PAH, polychlorinated aromatic hydrocarbons PCB77, 3,4,3′,4′-tetrachlorobiphenyl Immunotoxicity TBBP A-PE, tetrabromobisphenol A-bis-(2,3-dibromopropylether) Polybrominated flame retardants PBF, polybrominated flame retardants TBBP A, tetrabromobisphenol A Laser scanning cytometry CYP 1A1, cytochrome P450 1A1 MTT, 3(4,5-dimethyl-thiazoyl-2-yl)2,5-diphenyl-tetrazolium bromide IL-2 receptor α chain (CD25) Cytochrome P450 1A1 Con A, concanavalin A TBBP A-AE, tetrabromobisphenol A-bisallylether EROD, ethoxyresorufin- o-deethylase TCDD, 2,3,7,8-tetrachlorodibenzo- p-dioxin TBP, 2,4,6-tribromophenol DBDE, decabromodiphenylether MC, 3-methylcholanthrene Ah receptor, aryl hydrocarbon receptor CD25, interleukin-2 receptor α chain Ah-receptor Immunopathology Toxicity Cytochrome P450 Cytokine Rodentia Flame retardant Splenocyte In vitro Ah receptor Vertebrata Mammalia Hepatocyte Interleukin 2 Mouse Animal Alpha-Peptide chain Bromine Organic compounds IL-2 receptor 7 chain (CD25) Mechanism of action
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Summary:	Polybrominated flame retardants (PBF) are frequently used additives in electronical equipment. They are ubiquitous environmental contaminants which bioaccumulate with several health effects for humans and the environment. This study investigated immunotoxic effects of the PBF tetrabromobisphenol A (TBBP A), tetrabromobisphenol A-bisallylether (TBBP A-AE), tetrabromobisphenol A-bis-(2,3-dibromopropyl-ether) (TBBP A-PE), decabromodiphenylether (DBDE), and 2,4,6-tribromophenol (TBP) in vitro . The structurally related polychlorinated aromatic hydrocarbon 3,4,3′,4′-tetrachlorobiphenyl (PCB77) and dioxins mediate their immunotoxicity via the Ah-receptor gene complex. A highly relevant function of the Ah receptor, the induction of CYP 1A1 in hepatocytes of C57BL/6 mice by the established inducers 3-methylcholanthrene (MC) and PCB77 was compared to the effect of PBF by measurement of ethoxyresorufin- o-deethylase (EROD) activity. The PBF did not show any induction of CYP 1A1, while EROD activity of hepatocytes exposed to MC and PCB77 was induced 10.8- and 8.7-fold, respectively. To investigate immunotoxic effects of the flame retardants, splenocytes of C57BL/6 mice were incubated with subtoxic doses of the flame retardants and PCB77 and activated by concanavalin A (Con A). The flame retardants TBBP A and TBBP A-AE significantly inhibited the expression of interleukin-2 receptor α chain (CD25) in contrast to TBBP A-PE, DBDE, TBP, and PCB77 as shown by immunohistochemistry and quantitative analysis by laser scanning cytometry. None of the substances had any effect on the Con A-induced production of cytokines. Hence, TBBP A and TBBP A-AE may act as immunotoxic compounds by specifically inhibiting the expression of CD25.
Bibliography:	ObjectType-Article-2 SourceType-Scholarly Journals-1 ObjectType-Feature-1 content type line 23
ISSN:	0300-483X 1879-3185
DOI:	10.1016/S0300-483X(02)00442-0