ToxSci Advance Access originally published online on February 19, 2004
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Toxicological Sciences 79, 98-105 (2004)
Toxicological Sciences vol. 79 no. 1 © Society of Toxicology; all rights reserved.
Altered AP-1 (Activating Protein-1) Activity and c-jun Activation in T Cells Exposed to the Amide Class Herbicide 3,4-Dichloropropionanilide (DCPA)
Department of Microbiology, Immunology and Cell Biology, Robert C. Byrd Health Sciences Center, West Virginia University, Morgantown, West Virginia 265069177
Received October 15, 2003; accepted January 24, 2004
3,4-Dichloropropionanilide (DCPA), the active ingredient of some postemergence herbicides, has been demonstrated to inhibit several immune system functions including cytokine production by T cells. The central role of cytokines in regulating the immune response suggests a possible mechanism by which DCPA inhibits the immune system. Since interleukin (IL)-2 is critical in regulating many immune functions, we chose to investigate the effect of DCPA on this cytokine. Using the human T lymphoma line, Jurkat, stimulated with phorbol-12-myristate acetate (PMA) and the calcium ionophore A23187 (Io), we determined that DCPA exposure decreased IL-2 secretion and mRNA levels in a dose dependent manner. We hypothesized that DCPA affected one or more of the transcription factors that regulate IL-2 gene transcription. Activating protein 1(AP-1) is a transcription factor that has been demonstrated to be required for optimal IL-2 gene transcription. Electrophoretic mobility shift assays (EMSAs) demonstrated a decreased level of AP-1 DNA binding activity in DCPA-exposed Jurkat cells compared to control cells from 30 min to 2 h after stimulation. The altered AP-1 DNA binding kinetics was associated with a decrease in c-jun protein in these cells at 1 and 2 h after exposure and a decreased level of phosphorylated c-jun at 14 h after exposure. These results suggest a possible mechanism for DCPA-induced IL-2 inhibition; alteration in the activation of the c-jun component of AP-1.
Key Words: 3,4-dichloropropionanilide; AP-1; c-jun; IL-2; T cell; propanil.
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