Gender differences in autoimmune diseases: estrogen increases calcineurin expression in systemic lupus erythematosus.
Systemic lupus erythematosus (SLE) predominantly affects women (9:1 compared to men) of childbearing age and often decreases its intensity in postmenopausal women, suggesting that sex hormones play a role in its pathogenesis. Comparison of steady-state levels of calcineurin mRNA using RNase protection assays revealed increased calcineurin expression in response to estradiol in cultured T cells from nine female lupus patients. Calcineurin mRNA levels did not increase significantly in T cells from eight age-matched normal control female volunteers. Estrogen-dependent calcineurin mRNA increased in a dose-dependent fashion, while progesterone and dexamethasone did not increase calcineurin mRNA in patient cells. Lupus T cell calcineurin mRNA increased in response to estradiol at 6 h but not at 3 h. Calcineurin phosphatase activity increased in lupus T cell extracts after incubation of cells with estradiol, while phosphatase activity in normal T cells was unaffected by estrogen. Calcineurin expression in T cells from patients with vasculitis and rheumatoid arthritis taking medications similar to those taken by the lupus patients was unaffected by estradiol. This study provides the first evidence for a molecular marker of estrogen action in lupus patients and suggests that estrogen-dependent changes in lupus T cell calcineurin could alter proinflammatory cytokine gene regulation and T-B cell interactions.
Rider
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School of Biological Sciences, University of Missouri-Kansas City, Kansas City, Missouri, 64110, USA.
Foster
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RT
Evans
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M
Suenaga
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R
Abdou
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NI
D000328:Adult; D001327:Autoimmune Diseases / Q000503:physiopathology*; D019703:Calcineurin / Q000235:genetics / Q000494:pharmacology; D002478:Cells, Cultured; D003470:Culture Media; D004305:Dose-Response Relationship, Drug; D004958:Estradiol / Q000494:pharmacology; D004967:Estrogens / Q000494:pharmacology; D005260:Female; D015870:Gene Expression / Q000187:drug effects; D006801:Humans; D008180:Lupus Erythematosus, Systemic / Q000235:genetics; D008213:Lymphocyte Activation; D008297:Male; D012333:RNA, Messenger / Q000378:metabolism; D012727:Sex Characteristics; D012744:Sex Ratio; D013601:T-Lymphocytes / Q000166:cytology / Q000276:immunology; D013997:Time Factors
D003470:Culture Media; D004967:Estrogens; D012333:RNA, Messenger; D004958:Estradiol; D019703:Calcineurin