Genistein reverses diminished T-cell signal transduction, induced by post-menopausal estrogen levels.
OBJECTIVE
This study addressed the ability of genistein to reverse the loss of T-cell signaling components, induced by estrogen deficiency associated with aging.


METHODS
Using Jurkat 6.1 T cells, genistein regulation of CD3zeta, JAK3, and NFkappaB was analysed by Western immunoblotting at 4 or 40 pg/mL (post- and pre-menopausal levels, respectively) estradiol (E(2)). Corresponding gene expressions were quantified by real-time polymerase chain reaction (RT-PCR). For functionality, levels of IL-2 were correlated with its transcription by RT-PCR.


RESULTS
At 4 pg/mL E(2), signaling proteins were decreased compared with 40 pg/mL: CD3zeta, 1.58-fold; JAK3, 1.75-fold; and NFkappaB, 1.73-fold (P < 0.001). Genistein, at 0.5 and 5.0 microm, added to 4 pg/mL E(2) induced their expression to 40 pg/mL levels. While significantly diminished IL-2 mRNA levels were observed at 4 pg/mL E(2), genistein induced IL-2 mRNA to 40 pg/mL levels.


CONCLUSIONS
Genistein restores CD3zeta, NFkappaB and JAK3 proteins and mRNAs at post-meonopausal estrogen levels, in vitro, with no significant effect at pre-menopausal estrogen levels.
Parry
J Preston
JP
Division of Reproductive Endocrinology and Infertility, Department of Obstetrics, Gynecology, and Women's Health, University of Louisville School of Medicine, Louisville, KY 40202, USA.
Taylor
Douglas D
DD
Nakajima
Steven T
ST
Gercel-Taylor
Cicek
C
D017252:CD3 Complex / Q000276:immunology; D004967:Estrogens / Q000097:blood*; D005260:Female; D019833:Genistein / Q000494:pharmacology*; D006801:Humans; D007376:Interleukin-2 / Q000096:biosynthesis; D053616:Janus Kinase 3 / Q000378:metabolism; D019169:Jurkat Cells; D008213:Lymphocyte Activation / Q000187:drug effects; D016328:NF-kappa B / Q000378:metabolism; D017698:Postmenopause / Q000187:drug effects* / Q000276:immunology*; D015398:Signal Transduction / Q000187:drug effects*; D013601:T-Lymphocytes / Q000187:drug effects* / Q000276:immunology*
D017252:CD3 Complex; D004967:Estrogens; D007376:Interleukin-2; D016328:NF-kappa B; D019833:Genistein; C507933:JAK3 protein, human; D053616:Janus Kinase 3