title: Estradiol differentially regulates calreticulin: a potential link with abnormal T cell function in systemic lupus erythematosus?
abstract: OBJECTIVE
  Systemic lupus erythematosus (SLE) is an autoimmune disease that affects women nine times more often than men. The present study investigates estradiol-dependent control of the calcium-buffering protein, calreticulin, to gain further insight into the molecular basis of abnormal T cell signaling in SLE T cells.
  
  
  METHODS
  T cells were purified from blood samples obtained from healthy females and SLE patients. Calreticulin expression was quantified by real-time polymerase chain amplification. Calreticulin and estrogen receptor-α were co-precipitated and analyzed by Western blotting to determine if the proteins associate in T cells.
  
  
  RESULTS
  Calreticulin expression increased (p = 0.034) in activated control T cells, while estradiol decreased (p = 0.044) calreticulin in resting T cells. Calreticulin expression decreased in activated SLE T cell samples and increased in approximately 50% of resting T cell samples. Plasma estradiol was similar (p > 0.05) among SLE patients and control volunteers. Estrogen receptor-α and calreticulin co-precipitated from nuclear and cytoplasmic T cell compartments.
  
  
  CONCLUSIONS
  The results indicate that estradiol tightly regulates calreticulin expression in normal human T cells, and the dynamics are different between activated and resting T cells. The absence of this tight regulation in SLE T cells could contribute to abnormal T cell function.
authors.affiliation: Department of Biology, Pittsburg State University, Pittsburg, Kansas 66762, USA.
authors.forename: J M
authors.initials: JM
authors.lastname: Ward
authors.forename: V
authors.initials: V
authors.lastname: Rider
authors.forename: N I
authors.initials: NI
authors.lastname: Abdou
authors.forename: B
authors.initials: B
authors.lastname: Kimler
mesh_terms: D000328:Adult; D015153:Blotting, Western; D037282:Calreticulin / Q000378:metabolism*; D016022:Case-Control Studies; D004958:Estradiol / Q000378:metabolism*; D047628:Estrogen Receptor alpha / Q000378:metabolism; D005260:Female; D005786:Gene Expression Regulation; D006801:Humans; D008180:Lupus Erythematosus, Systemic / Q000453:epidemiology / Q000503:physiopathology*; D008875:Middle Aged; D060888:Real-Time Polymerase Chain Reaction; D012737:Sex Factors; D015398:Signal Transduction; D013601:T-Lymphocytes / Q000378:metabolism / Q000473:pathology*
chemical_list: D037282:Calreticulin; D047628:Estrogen Receptor alpha; D004958:Estradiol
keywords: SLE; calreticulin; estradiol; estrogen receptor-α; human T cells
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