Stressor: 4




Stressor Overview


AOPs Including This Stressor


Events Including This Stressor


Chemical Table


User term DTXID Preferred name Casrn jchem_inchi_key indigo_inchi_key

AOP Evidence


Binding to estrogen receptor (ER)-α in immune cells leading to exacerbation of systemic lupus erythematosus (SLE)

There is no evidence text for this AOP

Event Evidence


Binding to estrogen receptor (ER)-α in immune cells

There is no evidence text for this event.

Induction of GATA3 expression

Expression of GATA3 was induced in CD4+T cells treated with E2 at a concentration of 10-9 M (272.4 pg/mL) for 12-16 hours (Lambert KC. 2005).  GATA3 expression has potential to induced IL-4 production in CD4+T cell.  In contrast, expression of T-bet was decreased, which means E2 skew the immune system from a Th1 to a Th2 profile (Lambert KC. 2005).

Increase of Th2 cells producing IL-4

In vitro, the addition of E2 significantly increased IL-4 secretion from ERα-replete CD4+T cells, while this effect was abrogated in ERα-deficient CD4+T cells. (Lambert KC. 2005).

Increase of anti-DNA antibody from autoreactive B cell

BPA as well as E2 and diethylstilbestrol (DES) enhanced anti-Br-RBC autoantibody production by B1 cells in vivo.  IgM production by B1 cells in the presence of ED was more prominent on aged BWF1 mice developing lupus nephritis. (Yurino H. 2004). 

To examine a direct effect of endocrine disruptors on IgM antibody production by B1 or B2 cells, B1 cells were prepared from peritoneal cells and B2 cells from spleen, B1 or B2 cells were cultured in the presence of endocrine disruptors (E2: 100 nM, DES: 100 nM, BPA: 1 μM) for 4 days (Yurino H. 2004). 

Direct exposure of PBMCs from SLE patients to E2 induces secretion of anti-dsDNA antibodies and enhances the secretion of Igs, in particular IgG (Kanda N. 1999).

In both (NZB×NZW) F1 and MRL/lpr mice, estrogen treatment exacerbates the lupus disease, with augmented levels of autoantibodies against dsDNA and phospholipids as well as formation of circulating immune complexes (Grimaldi CM. 2002, Peeva E. 2000).

Hybridomas generated from E2-treated mice express high-affinity, unmutated anti-DNA antibodies, indicating that naı¨ve B cells that are normally deleted or anergized are rescued from tolerance induction (Bynoe MS. 2000).  E2 treatment resulted in a rise in anti-DNA serum titers and in Ig deposition in renal glomeruli (Bynoe MS. 2000).

Exacerbation of systemic lupus erythematosus (SLE)

The NZB/W F1 mouse is the oldest classical model of lupus generated by the F1 hybrid between the NZB and NZW strains.  In both NZB/W F1 and MRL/lpr mice, estrogen treatment exacerbates the lupus disease (Grimaldi CM. 2002, Peeva E. 2000).  In postmenopausal women there was an increase in number of mild flares in women receiving estrogen supplementation suggesting that the addition of estrogen to a low estrogen state enhances flare rate (Buyon JP. 1998).

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Characterization of Exposure