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鼠脾细胞和脾B细胞的脂多糖激活增加了芳烃受体和芳烃受体核转运蛋白的表达。

Lipopolysaccharide activation of murine splenocytes and splenic B cells increased the expression of aryl hydrocarbon receptor and aryl hydrocarbon receptor nuclear translocator.

作者信息

Marcus R S, Holsapple M P, Kaminski N E

机构信息

Department of Pharmacology and Toxicology, Michigan State University, East Lansing, Michigan, USA.

出版信息

J Pharmacol Exp Ther. 1998 Dec;287(3):1113-8.

PMID:9864300
Abstract

These studies characterized the profile of AhR and ARNT expression in primary splenocytes and purified splenic B cells after cellular activation with lipopolysaccharide (LPS). LPS treatment of mouse splenocytes markedly increased the magnitude of both AhR and ARNT steady state mRNA expression. AhR mRNA expression peaked at 8 hr post-LPS activation and was increased by approximately 5-fold compared with freshly isolated splenocytes (i.e., time 0). ARNT mRNA expression began to increase at 8 hr postactivation, peaked at approximately 48 hr and was increased by approximately 4-fold when compared with nonactivated splenocytes at time 0. Western blotting also demonstrated an increase in the relative magnitude of both the AhR and ARNT proteins in LPS activated splenocytes. Likewise, the presence of the AhR, ARNT and cytochrome P450IA1 (CYP1A1) proteins were also detected in purified primary splenic B cells, and the magnitude of protein expression was enhanced in LPS activated splenic B cells at 12 and 24 hr relative to time matched controls for each of these proteins. In summary, these findings suggest that on LPS activation the magnitude of AhR and ARNT mRNA and protein increases in both splenocytes and purified primary splenic B cells. Moreover, because the increase in the relative magnitude of CYP1A1 protein in response to LPS occurred in the absence of exogenous AhR ligand, these results suggest that B-cell activation is sufficient to induce AhR nuclear translocation and binding to dioxin-responsive elements in the promoter region of AhR-responsive genes.

摘要

这些研究描绘了在用脂多糖(LPS)激活细胞后,原代脾细胞和纯化的脾B细胞中芳烃受体(AhR)和芳香烃受体核转运蛋白(ARNT)的表达情况。用LPS处理小鼠脾细胞显著增加了AhR和ARNT稳态mRNA表达的水平。AhR mRNA表达在LPS激活后8小时达到峰值,与新鲜分离的脾细胞(即时间0)相比增加了约5倍。ARNT mRNA表达在激活后8小时开始增加,在约48小时达到峰值,与时间0时未激活的脾细胞相比增加了约4倍。蛋白质印迹法也显示LPS激活的脾细胞中AhR和ARNT蛋白的相对水平增加。同样,在纯化的原代脾B细胞中也检测到了AhR、ARNT和细胞色素P450IA1(CYP1A1)蛋白的存在,并且在LPS激活的脾B细胞中,相对于这些蛋白各自的时间匹配对照,在12小时和24小时时蛋白表达水平增强。总之,这些发现表明,在LPS激活后,脾细胞和纯化的原代脾B细胞中AhR和ARNT的mRNA和蛋白水平均增加。此外,由于在没有外源性AhR配体的情况下,LPS诱导的CYP1A1蛋白相对水平增加,这些结果表明B细胞激活足以诱导AhR核转位并与AhR反应基因启动子区域中的二噁英反应元件结合。

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