17-beta-estradiol suppresses IL-2 and IL-2 receptor.
Interleukin-2 (IL-2) plays an important role in adaptive immune responses. These responses differ between females and males and may be due to the sex steroid estrogen. In this investigation we show that estrogen suppresses IL-2 production from activated peripheral blood T cells and CD4+ T cell lines at the transcriptional level. Suppression of IL-2 occurred at short term, high 17-beta-estradiol concentrations as well as longer term lower 17-beta-estradiol concentrations. In CD4+ Jurkat T cells, suppression of IL-2 was associated with decreased nuclear binding of two important IL-2 promoter transcription factors: NFkappaB and AP-1. The decreased nuclear binding of NFkappaB occurred in the setting of estrogen-induced increases in IkappaBalpha protein levels, an important inhibitor of NFkappaB nuclear translocation. 17-beta-Estradiol was also shown to inhibit IL-2 receptor (IL-2R) expression in activated peripheral blood T cells. Estrogen-induced suppression of IL-2 and its receptor may have many ramifications for our understanding of immune and autoimmune sexual dichotomies, immune responses during pregnancy, and potential therapeutic intervention with hormone agonists and antagonists.
McMurray
R W
RW
Rheumatology Section, G.V. (Sonny) Montgomery VA Hospital, Jackson, MS 39216, USA. Robert.McMurray@med.va.gov
Ndebele
K
K
Hardy
K J
KJ
Jenkins
J K
JK
D021581:Active Transport, Cell Nucleus; D015153:Blotting, Western; D015496:CD4-Positive T-Lymphocytes / Q000378:metabolism; D002467:Cell Nucleus / Q000378:metabolism; D002478:Cells, Cultured; D004305:Dose-Response Relationship, Drug; D004797:Enzyme-Linked Immunosorbent Assay; D004958:Estradiol / Q000378:metabolism*; D004967:Estrogens / Q000378:metabolism; D005434:Flow Cytometry; D006801:Humans; D007376:Interleukin-2 / Q000037:antagonists & inhibitors / Q000378:metabolism*; D019169:Jurkat Cells; D008213:Lymphocyte Activation; D008214:Lymphocytes / Q000378:metabolism; D008297:Male; D016328:NF-kappa B / Q000378:metabolism; D011485:Protein Binding; D012333:RNA, Messenger / Q000378:metabolism; D015375:Receptors, Interleukin-2 / Q000037:antagonists & inhibitors / Q000378:metabolism*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D012737:Sex Factors; D013601:T-Lymphocytes / Q000378:metabolism; D013997:Time Factors
D004967:Estrogens; D007376:Interleukin-2; D016328:NF-kappa B; D012333:RNA, Messenger; D015375:Receptors, Interleukin-2; D004958:Estradiol