The flame retardants tetrabromobisphenol A and tetrabromobisphenol A-bisallylether suppress the induction of interleukin-2 receptor alpha chain (CD25) in murine splenocytes.
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The flame retardants tetrabromobisphenol A and tetrabromobisphenol A-bisallylether suppress the induction of interleukin-2 receptor alpha chain (CD25) in murine splenocytes. / Pullen, Sabine; Boecker, Ronald; Tiegs, Gisa.
in: TOXICOLOGY, Jahrgang 184, Nr. 1, 1, 2003, S. 11-22.Publikationen: SCORING: Beitrag in Fachzeitschrift/Zeitung › SCORING: Zeitschriftenaufsatz › Forschung › Begutachtung
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T1 - The flame retardants tetrabromobisphenol A and tetrabromobisphenol A-bisallylether suppress the induction of interleukin-2 receptor alpha chain (CD25) in murine splenocytes.
AU - Pullen, Sabine
AU - Boecker, Ronald
AU - Tiegs, Gisa
PY - 2003
Y1 - 2003
N2 - 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.
AB - 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.
KW - Animals
KW - Female
KW - Immunohistochemistry
KW - Mice
KW - Mice, Inbred C57BL
KW - Enzyme-Linked Immunosorbent Assay
KW - Microscopy, Confocal
KW - Cell Separation
KW - Cell Survival/drug effects
KW - Cytokines/metabolism
KW - Enzyme Induction/drug effects
KW - Cytochrome P-450 CYP1A1/biosynthesis
KW - Flame Retardants/toxicity
KW - Hepatocytes/drug effects
KW - Indicators and Reagents
KW - Interleukin-2/biosynthesis
KW - Polybrominated Biphenyls/toxicity
KW - Receptors, Interleukin-2/biosynthesis
KW - Solutions
KW - Spleen/cytology/drug effects/metabolism
KW - Tetrazolium Salts
KW - Thiazoles
KW - Animals
KW - Female
KW - Immunohistochemistry
KW - Mice
KW - Mice, Inbred C57BL
KW - Enzyme-Linked Immunosorbent Assay
KW - Microscopy, Confocal
KW - Cell Separation
KW - Cell Survival/drug effects
KW - Cytokines/metabolism
KW - Enzyme Induction/drug effects
KW - Cytochrome P-450 CYP1A1/biosynthesis
KW - Flame Retardants/toxicity
KW - Hepatocytes/drug effects
KW - Indicators and Reagents
KW - Interleukin-2/biosynthesis
KW - Polybrominated Biphenyls/toxicity
KW - Receptors, Interleukin-2/biosynthesis
KW - Solutions
KW - Spleen/cytology/drug effects/metabolism
KW - Tetrazolium Salts
KW - Thiazoles
M3 - SCORING: Journal article
VL - 184
SP - 11
EP - 22
JO - TOXICOLOGY
JF - TOXICOLOGY
SN - 0300-483X
IS - 1
M1 - 1
ER -