Functional activation of arylhydrocarbon receptor (AhR) in primary T cells by 2,3,7,8-tetrachlorodibenzo-p-dioxin.
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.
National Institute for Environmental Studies, 305-8506, Tsukuba, Ibaraki, Japan.
Hirotoshi
H
Doi
Tadashi
T
Baba
Chiharu
C
Tohyama
Keiko
K
Nohara
D000818:Animals; D051784:Aryl Hydrocarbon Receptor Nuclear Translocator; D001402:B-Lymphocytes / Q000187:drug effects / Q000378:metabolism; D002478:Cells, Cultured; D019363:Cytochrome P-450 CYP1A1 / Q000187:drug effects / Q000235:genetics / Q000378:metabolism; D004268:DNA-Binding Proteins; D004305:Dose-Response Relationship, Drug; D005260:Female; D005786:Gene Expression Regulation / Q000187:drug effects; D051379:Mice; D008810:Mice, Inbred C57BL; D000072317:Polychlorinated Dibenzodioxins / Q000633:toxicity*; D012333:RNA, Messenger / Q000187:drug effects / Q000378:metabolism; D018336:Receptors, Aryl Hydrocarbon / Q000187:drug effects* / Q000378:metabolism*; D013154:Spleen / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D013601:T-Lymphocytes / Q000187:drug effects / Q000378:metabolism*; D013950:Thymus Gland / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D014157:Transcription Factors / Q000187:drug effects / Q000235:genetics / Q000378:metabolism
C497397:Arnt protein, mouse; D004268:DNA-Binding Proteins; D000072317:Polychlorinated Dibenzodioxins; D012333:RNA, Messenger; D018336:Receptors, Aryl Hydrocarbon; D014157:Transcription Factors; D051784:Aryl Hydrocarbon Receptor Nuclear Translocator; D019363:Cytochrome P-450 CYP1A1