Coumestrol, bisphenol-A, DDT, and TCDD modulation of interleukin-2 expression in activated CD+4 Jurkat T cells.

Abstract

Endogenous estrogens are known to modulate several components of immune response, including interleukin-2 (IL-2) production. IL-2 is a cytokine that plays an important role in adaptive immune responses. These responses may be modulated by xenoestrogens such as coumestrol, bisphenol A (BPA), DDT, and TCDD. In this research, we examined the effects and potential mechanisms of action of these estrogenic compounds on IL-2 production in activated CD4+ Jurkat T cells. IL-2 production was analyzed by ELISA and Western Blot. At the transcriptional level, protein expression was examined by RT-PCR. Coumestrol, DDT and TCDD (but not BPA) significantly suppressed IL-2 production in activated CD4+ Jurkat T cells, at the transcriptional and translational levels. The transcriptional suppression of IL-2 was associated with decreased protein levels of NF-kappabeta, an important IL-2 positive transcription factor, without affecting the expression of Ikappa-Balpha protein expression, an important inhibitor of NF-kappabeta nuclear translocation. Although the direct mechanisms of xenoestrogens modulation of the immune system remain to be elucidated, coumestrol-, DDT- and TCDD-induced suppression of IL-2 may have ramifications for our understanding of the impact of xenoestrogens on health and disease.