Differential Expression of Estrogen Receptors in Women with Systemic Lupus Erythematosus
VIRGINIA RIDER, XIAOLAN LI, GREG PETERSON, JOYCE DAWSON, BRUCE F. KIMLER, and NABIH I. ABDOU
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-ß. Biological effects of estradiol are mediated through 2 receptor proteins, estrogen receptor-a (ER-a) and estrogen receptor-ß (ER-ß). 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-a or ER-ß-specific agonists. Receptor activation was measured by increased expression of the T cell activation markers CD154 and calcineurin.
Results. Although the amount of ER-a 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-ß was similar in SLE and control T cells. The expression of ER-a or ER-ß 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-a and ER-ß agonists.
Conclusion. 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-a in SLE T cells suggests this receptor subtype participates in the sensitivity of SLE T cells to estrogen. (J Rheumatol 2006;33:1093–101)
Key Indexing Terms:
SYSTEMIC LUPUS ERYTHEMATOSUS
From the Department of Biology, Pittsburg State University, Pittsburg, Kansas, USA; Department of Dermatology and Rheumatology, Kunming Medical College, Kunming, People's Republic of China; Department of Radiation Oncology, University of Kansas Medical Center; and Center of Rheumatic Diseases, Allergy-Immunology, Kansas City, Missouri, USA.
Supported in part by NIH grant AI49272 and RR-16475 from the INBRE Program of the National Center for Research Resources; the Evans Memorial fund; and private funds from the Center for Rheumatic Diseases.
V. Rider, PhD, Department of Biology, Pittsburg State University; X. Li, MD, Department of Biology, Pittsburg State University, and Department of Dermatology and Rheumatology, Kunming Medical College; G. Peterson, MS; J. Dawson, MSN, Department of Biology, Pittsburg State University; B.F. Kimler, PhD, Department of Radiation Oncology, University of Kansas Medical Center; N.I. Abdou, MD, PhD, Center of Rheumatic Diseases, Allergy-Immunology.
Address reprint requests to Dr. V. Rider, Department of Biology, Pittsburg State University, Pittsburg, Kansas 66762. E-mail: firstname.lastname@example.org
Accepted for publication February 24, 2006.