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.
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-12myristate-13-acetate/i6nomycin (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-kappaB 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.
Han
S H
SH
Department of Biological Sciences, Korea Advanced Institute of Science and Technology, Taejon, South Korea.
Jeon
Y J
YJ
Yea
S S
SS
Yang
K H
KH
D016604:Aflatoxin B1 / Q000494:pharmacology*; D000818:Animals; D004268:DNA-Binding Proteins / Q000378:metabolism* / Q000502:physiology; D015536:Down-Regulation; D005260:Female; D005786:Gene Expression Regulation / Q000187:drug effects*; D017930:Genes, Reporter; D006801:Humans; D007376:Interleukin-2 / Q000235:genetics* / Q000378:metabolism; D019169:Jurkat Cells; D051379:Mice; D016328:NF-kappa B / Q000378:metabolism / Q000502:physiology; D050778:NFATC Transcription Factors; D009687:Nuclear Proteins; D012333:RNA, Messenger / Q000378:metabolism; D018808:Transcription Factor AP-1 / Q000378:metabolism* / Q000502:physiology; D014157:Transcription Factors / Q000378:metabolism* / Q000502:physiology; D014407:Tumor Cells, Cultured
D004268:DNA-Binding Proteins; D007376:Interleukin-2; D016328:NF-kappa B; D050778:NFATC Transcription Factors; D009687:Nuclear Proteins; D012333:RNA, Messenger; D018808:Transcription Factor AP-1; D014157:Transcription Factors; D016604:Aflatoxin B1