Abstract
Introduction: Systemic lupus erythematosus (SLE) is a chronic inflammatory autoimmune disease that affects various body systems, including the skin and facial features. Estrogen promotes lupus in human and mouse models of SLE. In this study, we conducted an in vivo study to investigate the relationship between two estrogen receptors (ERα and ERβ) and platelet-activating factor acetylhydrolase (PAF-AH) on the symptoms of SLE. Methods: Skin and facial features, serum PAF-AH activity, tumor-necrosis factor-alpha (TNF-α), and anti-double stranded DNA (anti-dsDNA) antibody titer, all of which are central to the classification and pathogenesis of SLE, were measured in SLE model mice injected with various ER antagonists. Results: In SLE mice, the injection of an ERβ antagonist 4-[2-phenyl-5,7-bis(trifluoromethyl)pyrazolo[1,5-α]pyrimidine-3-yl]-phenol induced the expression of facial erythema (especially around a cheek). The injection of an ERα/β antagonist tamoxifen induced hair-loss on the head and the neck. The injection of an ERα antagonist methylpiperidino pyrazole or tamoxifen increased PAF-AH activity and decreased TNF-α levels and anti-dsDNA antibody in mouse serum. Conclusions: The activation of ERα and inactivation of ERβ can cause inflammatory and cutaneous symptoms of SLE, respectively, implying that ERα antagonists and/or ERβ agonists can be useful for the prevention and treatment of SLE.
