Suppression of the interleukin-2 gene expression by aflatoxin B1 is mediated through the down-regulation of the NF-AT and AP-1 transcription factors

Seung Hyun Han, Young Jin Jeon, Sung Su Yea, Kyu Hwan Yang

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26 Scopus citations

Abstract

The effect of aflatoxin B1 (AFB1) on the interleukin-2 (IL-2) gene expression was investigated in thymocytes of B6C3F1 mice, Jurkat E6-1 human T-cell leukemia, and EL4.IL-2 murine thymoma. AFB1 inhibited the phorbol-12-myristate-13-acetate/ionomycin (PMA/Io)-induced IL-2 mRNA expression in the murine thymocytes and Jurkat E6-1 cells as determined by qualitative RT-PCR, while no effect was observed in the EL4.IL-2 cells. Electrophoretic mobility shift assay indicated that AFB1 treatment showed an inhibition of the NF-AT and AP-1 DNA binding in PMA/Io-stimulated thymocytes and Jurkat E6-1 cells. No effect was observed on the Oct and NF-κB DNA binding. Employing a reporter gene expression system with p(NF-AT)3-CAT and p(AP-1)3-CAT, treatment with AFB1 to the transfected Jurkat E6-1 cells also showed an inhibition of the PMA/Io-induced NF-AT/CAT and AP-1/CAT activities. These results suggest that suppression of the IL-2 gene expression by AFB1 is mediated through the down-regulation of the NF-AT and AP-1 activation. Copyright (C) 1999 Elsevier Science Ireland Ltd.

Original languageEnglish (US)
Pages (from-to)1-10
Number of pages10
JournalToxicology Letters
Volume108
Issue number1
DOIs
StatePublished - Jul 30 1999

Bibliographical note

Funding Information:
This work was supported by the grant from the Ministry of Science and Technology, ROK. We thank Dr Norbert E. Kaminski at Michigan State University for critical comments on the manuscripts

Keywords

  • AP-1
  • Aflatoxin B
  • Immunosuppression
  • Interleukin-2
  • NF-AT

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