The amide-class herbicide, propanil, causes numerous immunomodulary effects in animal models. In the present study, we investigated the effect of propanil on IL-2 expression and production in the murine lymphoma T cell line, EL-4. When supernatants of cells stimulated with phorbol 12-myristate 13-acetate in the presence of propanil were assessed by enzyme-linked immunosorbent assay, IL-2 levels were dose-dependently decreased by 20 and 50 microM of propanil but not at 10 microM. Quantitative Northern blot analysis of peak IL-2 message levels also showed a dose-dependent decrease. The kinetic pattern of message production, however, was unaffected. To determine if the reduced message production was due to reduced signaling or message stability, nuclear run-on and mRNA stability assays were performed. Nuclear run-on assays determined that the transcription rate of the IL-2 gene was decreased approximately 50% in the presence of 20 microM propanil, indicating that it was able to interfere with signal transduction. IL-2 message stability assays also demonstrated a reduction in message stability. Thus, propanil appears to reduce IL-2 production by affecting the signal transduction pathway and IL-2 message stability.
Copyright 1999 Academic Press.