Document Detail

2,3,7,8-Tetrachlorodibenzo-p-dioxin modulates the expression of cKrox and Runx3, transcription regulatory factors controlling the lineage commitment of CD4+CD8+ into CD4 and CD8 thymocytes, respectively.
MedLine Citation:
PMID:  18602973     Owner:  NLM     Status:  MEDLINE    
2,3,7,8-Tetrachlorodibenzo-p-dioxin (TCDD) was reported to skew the lineage commitment of thymocytes toward CD4(-)CD8+ T (CD8 T) cells. However, the underlying mechanisms are not known. In the present study, we first demonstrated that the expression of transcription regulatory factors such as cKrox and Runx3, which have been shown to be intimately associated with the commitment of CD4+CD8+ double-positive (DP) to CD4 or CD8 single-positive (SP) thymocyes, was down-regulated by TCDD in CD4 SP thymocytes, but up-regulated in DP, CD4+CD8+ double-negative (DN), and CD8 SP thymocytes. Then, we found that TCDD inhibited the differentiation of DPK cells, an immature CD4+CD8+ lymphoma cell line, into CD4+CD8(-) T cells, as well as the expression of cKrox and Runx3 upon antigen stimulation. Co-treatment with the AhR antagonist alpha-naphthoflavone did not completely block the inhibitory action of TCDD on DPK differentiation and the expression of cKrox and Runx3 in DPK cells, suggesting that the immunomodulatory abilities of TCDD are produced, at least in part, independently of the AhR pathway in DPK cells. Our findings could help in understanding the regulatory mechanisms of TCDD on thymocyte development, in particular on the skewed differentiation of DP into CD8 SP thymocytes.
Byoung-Chul Gill; Chang-Hwan Jeon; Ha-Na Sung; Hye-Lin Kim; Dah-Won Jin; Joo-Hung Park
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't     Date:  2008-06-17
Journal Detail:
Title:  Toxicology letters     Volume:  180     ISSN:  0378-4274     ISO Abbreviation:  Toxicol. Lett.     Publication Date:  2008 Aug 
Date Detail:
Created Date:  2008-08-25     Completed Date:  2008-11-06     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  7709027     Medline TA:  Toxicol Lett     Country:  Netherlands    
Other Details:
Languages:  eng     Pagination:  189-95     Citation Subset:  IM    
Department of Biology, Changwon National University, #9 Sarim-dong, Changwon 641-773, Kyungnam, South Korea.
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MeSH Terms
Benzoflavones / pharmacology
CD4-Positive T-Lymphocytes / drug effects,  metabolism*
CD8-Positive T-Lymphocytes / drug effects,  metabolism*
Cell Differentiation / drug effects
Cell Lineage / drug effects,  genetics*
Core Binding Factor Alpha 3 Subunit / biosynthesis*
DNA-Binding Proteins / biosynthesis*
Down-Regulation / drug effects
Environmental Pollutants / toxicity*
Flow Cytometry
Mice, Inbred BALB C
Receptors, Aryl Hydrocarbon / drug effects
Reverse Transcriptase Polymerase Chain Reaction
Tetrachlorodibenzodioxin / pharmacology*
Transcription Factors / biosynthesis*
Reg. No./Substance:
0/Benzoflavones; 0/Core Binding Factor Alpha 3 Subunit; 0/DNA-Binding Proteins; 0/Environmental Pollutants; 0/Receptors, Aryl Hydrocarbon; 0/Runx3 protein, mouse; 0/Transcription Factors; 0/Zbtb7b protein, mouse; 1746-01-6/Tetrachlorodibenzodioxin; 604-59-1/alpha-naphthoflavone

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