The flame retardants tetrabromobisphenol A and tetrabromobisphenol A-bisallylether suppress the induction of interleukin-2 receptor alpha 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 (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 alpha 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.
Pullen
Sabine
S
Institute of Experimental and Clinical Pharmacology and Toxicology, University of Erlangen-Nuremberg, Erlangen, Germany.
Boecker
Ronald
R
Tiegs
Gisa
G
D000818:Animals; D002469:Cell Separation; D002470:Cell Survival / Q000187:drug effects; D019363:Cytochrome P-450 CYP1A1 / Q000096:biosynthesis; D016207:Cytokines / Q000378:metabolism; D004790:Enzyme Induction / Q000187:drug effects; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D005411:Flame Retardants / Q000633:toxicity*; D022781:Hepatocytes / Q000187:drug effects; D007150:Immunohistochemistry; D007202:Indicators and Reagents; D007376:Interleukin-2 / Q000096:biosynthesis*; D051379:Mice; D008810:Mice, Inbred C57BL; D018613:Microscopy, Confocal; D011075:Polybrominated Biphenyls / Q000633:toxicity*; D015375:Receptors, Interleukin-2 / Q000096:biosynthesis*; D012996:Solutions; D013154:Spleen / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D013778:Tetrazolium Salts; D013844:Thiazoles
D016207:Cytokines; D005411:Flame Retardants; D007202:Indicators and Reagents; D007376:Interleukin-2; D011075:Polybrominated Biphenyls; D015375:Receptors, Interleukin-2; D012996:Solutions; D013778:Tetrazolium Salts; D013844:Thiazoles; C471350:tetrabromobisphenol A-bisallylether; D019363:Cytochrome P-450 CYP1A1; C022616:thiazolyl blue; C020806:tetrabromobisphenol A