The induction of the lupus phenotype by estrogen is via an estrogen receptor-alpha-dependent pathway.
In order to investigate the roles of ER subtypes in the estrogen-induced lupus phenotype, ERalpha-deficient (ERalpha(-/-)) and wild-type mice (WT) were injected monthly with estradiol (E-2) starting at 8 weeks. In WT mice, E-2 treatment induced a lupus phenotype, with accelerated death and increased kidney damage, as well as Th2-type serum cytokine and autoantibody production. In contrast, only minimal changes were observed in ERalpha(-/-) mice after E-2 treatment. In a separate study, we found that in immune cells of autoimmune-prone SNF(1) and non-autoimmune DBF(1) mice, both ERalpha and ERbeta were differentially expressed and modulated by E-2. In SNF(1) mice, there were more CD4(+) and CD8(+) T cells constitutively expressing ERalpha, and the percentages of ERalpha+ dendritic cells and macrophages were increased after E-2 exposure compared to DBF(1) mice. Taken together, these observations strongly suggest a role for ERalpha in E-2-induced development of the lupus phenotype.
Feng
Feng
F
Department of Microbiology & Immunology, Cornell University, Ithaca, NY 14853, USA.
Nyland
Jennifer
J
Banyai
Michelle
M
Tatum
Arthur
A
Silverstone
Allen E
AE
Gavalchin
Jerrie
J
D000818:Animals; D001323:Autoantibodies / Q000097:blood / Q000276:immunology; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology / Q000378:metabolism; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology / Q000378:metabolism; D002469:Cell Separation; D016207:Cytokines / Q000096:biosynthesis / Q000276:immunology; D004797:Enzyme-Linked Immunosorbent Assay; D004958:Estradiol / Q000378:metabolism* / Q000494:pharmacology; D047628:Estrogen Receptor alpha / Q000378:metabolism*; D004967:Estrogens / Q000378:metabolism* / Q000494:pharmacology; D005434:Flow Cytometry; D008180:Lupus Erythematosus, Systemic / Q000276:immunology / Q000378:metabolism* / Q000473:pathology; D008181:Lupus Nephritis / Q000276:immunology / Q000473:pathology; D051379:Mice; D018345:Mice, Knockout; D010641:Phenotype
D001323:Autoantibodies; D016207:Cytokines; D047628:Estrogen Receptor alpha; D004967:Estrogens; D004958:Estradiol