GENDER DIFFERENCES IN AUTOIMMUNE-DISEASES - ESTROGEN INCREASES CALCINEURIN EXPRESSION IN SYSTEMIC LUPUS-ERYTHEMATOSUS

Systemic lupus erythematosus (SLE) predominantly affects women (9:1 co mpared to men) of childbearing age and often decreases its intensity i n postmenopausal women, suggesting that sex hormones play a role in it s pathogenesis. Comparison of steady-state levels of calcineurin mRNA using RNase protection assays revealed increased calcineurin expressio n 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. Estroge n-dependent calcineurin mRNA increased in a dose-dependent fashion, wh ile progesterone and dexamethasone did not increase calcineurin mRNA i n patient cells. Lupus T cell calcineurin mRNA increased in response t o estradiol at 6 h but not at 3 h. Calcineurin phosphatase activity in creased in lupus T cell extracts after incubation of cells with estrad iol, while phosphatase activity in normal T cells was unaffected by es trogen. Calcineurin expression in T cells from patients with vasculiti s and rheumatoid arthritis taking medications similar to those taken b y 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. (C) 1998 Academic Press.