Gender differences in autoimmune diseases: estrogen increases calcineurin expression in systemic lupus erythematosus

Clin Immunol Immunopathol. 1998 Nov;89(2):171-80. doi: 10.1006/clin.1998.4604.

Abstract

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Autoimmune Diseases / physiopathology*
  • Calcineurin / genetics
  • Calcineurin / pharmacology
  • Cells, Cultured
  • Culture Media
  • Dose-Response Relationship, Drug
  • Estradiol / pharmacology
  • Estrogens / pharmacology
  • Female
  • Gene Expression / drug effects
  • Humans
  • Lupus Erythematosus, Systemic / genetics
  • Lymphocyte Activation
  • Male
  • RNA, Messenger / metabolism
  • Sex Characteristics
  • Sex Ratio
  • T-Lymphocytes / cytology
  • T-Lymphocytes / immunology
  • Time Factors

Substances

  • Culture Media
  • Estrogens
  • RNA, Messenger
  • Estradiol
  • Calcineurin