Functional activation of arylhydrocarbon receptor (AhR) in primary T cells by 2,3,7,8-tetrachlorodibenzo-p-dioxin

被引:14
作者
Doi, H
Baba, T
Tohyama, C
Nohara, K
机构
[1] Natl Inst Environm Studies, Environm Hlth Sci Div, Tsukuba, Ibaraki 3050053, Japan
[2] Japan Sci & Technol, CREST, Kawagoe, Saitama 3320012, Japan
[3] Univ Tsukuba, Inst Appl Biochem, Tsukuba, Ibaraki 3058572, Japan
关键词
TCDD; CytochromCYPlAl; T cell; B cell;
D O I
10.1016/S0045-6535(03)00112-7
中图分类号
X [环境科学、安全科学];
学科分类号
08 ; 0830 ;
摘要
2,3,7,8-Tetrachlorodibenzo-p-dioxin (TCDD) exerts diverse adverse health effects by activating the transcription factor arylhydrocarbon receptor (AhR). The activated AhR induces the expression of various genes having xenobiotic responsive elements (XREs) in their enhancer regions, such as the gene for cytochrome P-450 1A1 (CYP1A1). The immune system is sensitively affected by TCDD, while the precise mechanism of how TCDD acts in each immune cell type remains to be determined. The results of previous studies on AhR activation in B cell lines, T cell clones, and thymocytes, which mainly consist of immature T cells, suggested that AhR in mature T cells is inactive, whereas that in B cells and immature T cells act functionally. In the present study, we investigated whether or not TCDD induces the CYP1A1 gene by functionally activating AhR in primary mature T cells in mice. When the splenocytes that contain mature T and B lymphocytes as their predominant cell types or the thymocytes were cultured in the presence of TCDD, each of them showed a similar magnitude of CYP1A1 induction with a peak induction at 4 h. Both mature T cells and B cells that had been separated from total splenocytes also showed CYP1A1 induction at the same magnitude with a peak induction at 4 h. Gene expression of CYP1A1 was observed at 0.1 nM or greater concentrations of TCDD in splenocytes and separated T cells. The induction of CYP1A1 in T cells was confirmed in mice exposed to TCDD. These results indicate that TCDD induces the functional activation of AhR in primary mature T cells in mice. (C) 2003 Elsevier Science Ltd. All rights reserved.
引用
收藏
页码:655 / 662
页数:8
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