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

Abstract

The effect of aflatoxin B-1 (AFB(1)) 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. AFB(1) 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 AFB(1) 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-kappa B DNA binding. Employing a reporter gene expression system with p(NF-AT)(3)-CAT and p(AP-1)(3)-CAT, treatment with AFB(1) 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 AFB, is mediated through the down-regulation of the NF-AT and AP-1 activation. (C) 1999 Elsevier Science Ireland Ltd. All rights reserved.