suppression of the inflammatory response in experimental arthritis is mediated via estrogen receptor α but not estrogen receptor β抑制炎症反应的实验性关节炎是通过雌激素受体α介导但不是雌激素受体β.pdfVIP

Dulos et al. Arthritis Research Therapy 2010, 12:R101 /content/12/3/R101 R E S E A R C H A R T I C L E Open Access Research article Suppression of the inflammatory response in experimental arthritis is mediated via estrogen receptor α but not estrogen receptor β John Dulos*, Peter Vijn, Cindy van Door n, Claudia L Hofstra, Desiree Veening-Griffioen, Jan de Graaf, Fred A Dijcks and Annemieke MH Boots Abstract Introduction: The immune modulatory role of estrogens in inflammation is complex. Both pro- and anti-inflammatory effects of estrogens have been described. Estrogens bind both estrogen receptor (ER)α and β. The contribution of ERα and ERβ to ER-mediated immune modulation was studied in delayed type hypersensitivity (DTH) and in experimental arthritis Methods: ER-mediated suppression of rat adjuvant arthritis (AA) was studied using ethinyl-estradiol (EE) and a selective ERβ agonist (ERB-79). Arthritis was followed for 2 weeks. Next, effects of ER agonists (ethinyl-estradiol, an ERα selective agonist (ERA-63) and a selective ERβ agonist (ERB-79) on the development of a tetanus toxoid (TT)-specific delayed type hypersensitivity response in wild type (WT) and in ERα - or ERβ-deficient mice were investigated. Finally, EE and ERA-63 were tested for their immune modulating potential in established collagen induced arthritis in DBA/1J mice. Arthritis was followed for three weeks. Joint pathology was examined by histology and radiology. Local synovial cytokine production was analyzed using Luminex technology. Sera were assessed for COMP as a biomarker of cartilage destruction. Results: EE was found to suppress clinical signs and symptoms in rat AA. The selective ERβ agonist ERB-79 had no effect on arthritis symptoms in this model. In the TT-specific DTH model, EE and the selective ERα agonist ERA-63 suppressed the TT-spec