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

Int J Environ Res Public Health. 2004 Mar;1(1):3-11. doi: 10.3390/ijerph2004010003.

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.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Benzhydryl Compounds
  • CD4-Positive T-Lymphocytes / cytology
  • CD4-Positive T-Lymphocytes / drug effects*
  • CD4-Positive T-Lymphocytes / metabolism
  • Coumestrol / pharmacology*
  • DDT / pharmacology*
  • Environmental Pollutants / pharmacology
  • Estrogens, Non-Steroidal / pharmacology
  • Gene Expression Regulation / drug effects*
  • Humans
  • Insecticides / pharmacology
  • Interleukin-2 / biosynthesis
  • Interleukin-2 / genetics
  • Interleukin-2 / metabolism*
  • Jurkat Cells
  • Lymphocyte Activation
  • NF-kappa B / metabolism
  • Phenols / pharmacology*
  • Polychlorinated Dibenzodioxins / pharmacology*
  • Protein Binding
  • RNA, Messenger / metabolism

Substances

  • Benzhydryl Compounds
  • Environmental Pollutants
  • Estrogens, Non-Steroidal
  • Insecticides
  • Interleukin-2
  • NF-kappa B
  • Phenols
  • Polychlorinated Dibenzodioxins
  • RNA, Messenger
  • DDT
  • bisphenol A
  • Coumestrol