Coumestrol, bisphenol-A, DDT, and TCDD modulation of interleukin-2 expression in activated CD+4 Jurkat T cells.
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.
Ndebele
Kenneth
K
Molecular Toxicology Research Laboratory, NIH Center for Environmental Health, School of Science and Technology, Jackson State University, Jackson, Mississippi, USA.
Tchounwou
Paul B
PB
McMurray
Robert W
RW
D001559:Benzhydryl Compounds; D015496:CD4-Positive T-Lymphocytes / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D003375:Coumestrol / Q000494:pharmacology*; D003634:DDT / Q000494:pharmacology*; D004785:Environmental Pollutants / Q000494:pharmacology; D004968:Estrogens, Non-Steroidal / Q000494:pharmacology; D005786:Gene Expression Regulation / Q000187:drug effects*; D006801:Humans; D007306:Insecticides / Q000494:pharmacology; D007376:Interleukin-2 / Q000096:biosynthesis / Q000235:genetics / Q000378:metabolism*; D019169:Jurkat Cells; D008213:Lymphocyte Activation; D016328:NF-kappa B / Q000378:metabolism; D010636:Phenols / Q000494:pharmacology*; D000072317:Polychlorinated Dibenzodioxins / Q000494:pharmacology*; D011485:Protein Binding; D012333:RNA, Messenger / Q000378:metabolism; D000098826:Bisphenol A Compounds
D001559:Benzhydryl Compounds; D003375:Coumestrol; D003634:DDT; D004785:Environmental Pollutants; D004968:Estrogens, Non-Steroidal; D007306:Insecticides; D007376:Interleukin-2; D016328:NF-kappa B; D010636:Phenols; D000072317:Polychlorinated Dibenzodioxins; D012333:RNA, Messenger; C006780:bisphenol A; D000098826:Bisphenol A Compounds