alpha-Naphthoflavone antagonism of 2,3,7,8-tetrachlorodibenzo-p-dioxin-induced murine lymphocyte ethoxyresorufin-O-deethylase activity and immunosuppression.
alpha-Naphthoflavone antagonism of 2,3,7,8-tetrachlorodibenzo-p-dioxin-induced murine lymphocyte ethoxyresorufin-O-deethylase activity and immunosuppression.
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发表时间：
1987-07
影响因子：
3.6
通讯作者：
J. A. Blank;A. N. Tucker;J. Sweatlock;T. Gasiewicz;M. Luster
中科院分区：
文献类型：
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作者：
J. A. Blank;A. N. Tucker;J. Sweatlock;T. Gasiewicz;M. Luster
2，3，7，8-四氯二苯并-对-二恶英（TCDD）在体内和体外均可抑制小鼠的体液免疫。研究表明，体液免疫的抑制是由Ah受体介导的。本文中提出的数据表明，α-萘酮（ANF）和β-萘酮（BNF），像TCDD，结合到大鼠和小鼠肝和小鼠脾细胞胞浆Ah受体。此外，BNF诱导细胞色素P1-450单加氧酶活性，通过乙氧基试卤灵-O-脱乙基酶（EROD）在小鼠脾细胞中的相同程度的TCDD。相反，ANF主要作用于拮抗TCDD诱导的脾细胞EROD活性。体外体液免疫试验表明，BNF与TCDD一样，具有抑制作用。而ANF在细胞毒性浓度下是抑制性的，较低浓度的ANF拮抗TCDD的抑制作用。ANF对TCDD诱导的EROD活性的拮抗作用和对体液免疫的抑制作用在相似浓度下发生。这些数据表明，ANF块TCDD抑制B淋巴细胞分化的竞争与TCDD的Ah受体的结合。由于TCDD毒性的机制还不完全清楚，ANF等探针可能在检查Ah受体介导毒性中的作用方面有很大的用处。
Suppression of murine humoral immunity by 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) has been shown to occur in vivo and in vitro. Studies have indicated that suppression of humoral immunity is mediated by the Ah receptor. Data presented in this paper demonstrate that alpha-naphthoflavone (ANF) and beta-naphthoflavone (BNF), like TCDD, bind to rat and murine hepatic and murine splenocyte cytosolic Ah receptor. Furthermore, BNF induces cytochrome P1-450 monooxygenase activity as measured by ethoxyresorufin-O-deethylase (EROD) in murine spleen cells to the same extent as TCDD. In contrast, ANF predominantly acts to antagonize TCDD induction of splenocyte EROD activity. Examination of humoral immunity in vitro demonstrated that BNF, like TCDD, is suppressive. Whereas ANF is suppressive at cytotoxic concentrations, lower concentrations of ANF antagonize the suppressive effect of TCDD. Antagonism by ANF of TCDD-induced EROD activity and suppression of humoral immunity occur at similar concentrations. These data suggest that ANF blocks TCDD suppression of B lymphocyte differentiation by competing with TCDD for binding to the Ah receptor. Since the mechanism of TCDD toxicity is not fully understood, probes such as ANF may be of great use in examining the role of the Ah receptor in mediating toxicity.