Differential expression of estrogen receptors in women with systemic lupus erythematosus.
OBJECTIVE
Systemic lupus erythematosus (SLE) is an autoimmune disease primarily affecting women. T cell activation markers (calcineurin, CD154) increase in SLE T cells cultured with estradiol 17-beta. Biological effects of estradiol are mediated through 2 receptor proteins, estrogen receptor-alpha (ER-alpha) and estrogen receptor-beta (ER-beta). We compared the amount of estrogen receptor subtypes in T cells and measured the ability of receptor agonist-specific ligands to activate marker gene expression.


METHODS
T cells were isolated from 22 female patients with SLE and 17 control women. The amount of ER subtypes was measured by immunoblotting. Some T cells were cultured with ER-alpha or ER-beta-specific agonists. Receptor activation was measured by increased expression of the T cell activation markers CD154 and calcineurin.


RESULTS
Although the amount of ER-alpha appeared to be less in SLE T cells than in control T cells, the difference was not statistically significant (p = 0.081). The quantity of ER-beta was similar in SLE and control T cells. The expression of ER-alpha or ER-beta was independent of menstrual cycle phase, age, or SLE disease activity. Calcineurin and CD154 expression increased in SLE T cells cultured in medium containing ER-alpha and ER-beta agonists.


CONCLUSIONS
These data indicate that both ER subtypes activate calcineurin and CD154 in SLE but not in normal T cells. Variation in the amount of ER-alpha in SLE T cells suggests this receptor subtype participates in the sensitivity of SLE T cells to estrogen.
Rider
Virginia
V
Department of Biology, Pittsburg State University, Kansas 66762, USA. vrider@pittstate.edu
Li
Xiaolan
X
Peterson
Greg
G
Dawson
Joyce
J
Kimler
Bruce F
BF
Abdou
Nabih I
NI
D000199:Actins / Q000494:pharmacology; D000328:Adult; D015415:Biomarkers / Q000378:metabolism; D015153:Blotting, Western; D023201:CD40 Ligand / Q000378:metabolism; D019703:Calcineurin / Q000378:metabolism; D002478:Cells, Cultured; D047628:Estrogen Receptor alpha / Q000819:agonists / Q000378:metabolism*; D047629:Estrogen Receptor beta / Q000819:agonists / Q000378:metabolism*; D005260:Female; D006304:Health Status; D006801:Humans; D008180:Lupus Erythematosus, Systemic / Q000276:immunology / Q000378:metabolism* / Q000503:physiopathology; D008213:Lymphocyte Activation / Q000187:drug effects; D008597:Menstrual Cycle / Q000276:immunology / Q000378:metabolism; D008875:Middle Aged; D012720:Severity of Illness Index; D013601:T-Lymphocytes / Q000187:drug effects / Q000276:immunology / Q000378:metabolism*
D000199:Actins; D015415:Biomarkers; D047628:Estrogen Receptor alpha; D047629:Estrogen Receptor beta; D023201:CD40 Ligand; D019703:Calcineurin