||G-protein-coupled estrogen recepter agonist suppresses airway inflammation in a mouse model of asthma through IL-10
G 蛋白共役エストロゲン受容体アゴニストは喘息モデルマウスに対して IL-10 を介し気道炎症を抑制する
糸賀, 正道ITOGA, Masamichi
Estrogen influences the disease severity and sexual dimorphism in asthma, whichis caused by complex mechanisms. Besides classical nuclear estrogen receptors (ERα/β),G-protein-coupled estrogen receptor (GPER) was recently established as an estrogenreceptor on the cell membrane. Although GPER is associated with immunoregulatoryfunctions of estrogen, the pathophysiological role of GPER in allergic inflammatorylung disease has not been examined. We investigated the effect of GPER-specificagonist G-1 in asthmatic mice. GPER expression in asthmatic lung was confirmed byimmunofluorescent staining. OVA-sensitized BALB/c and C57BL/6 mice were treatedwith G-1 by daily subcutaneous injections during an airway challenge phase, followedby histological and biochemical examination. Strikingly, administration of G-1attenuated airway hyperresponsiveness, accumulation of inflammatory cells, and levelsof Th2 cytokines (IL-5 and IL-13) in BAL fluid. G-1 treatment also decreased serumlevels of anti-OVA IgE antibodies. The frequency of splenic Foxp3+CD4+ regulatory Tcells and IL-10-producing GPER+CD4+ T cells was significantly increased inG-1-treated mice. Additionally, splenocytes isolated from G-1-treated mice showedgreater IL-10 production. G-1-induced amelioration of airway inflammation and IgEproduction were abolished in IL-10-deficient mice. Taken together, these resultsindicate that extended GPER activation negatively regulates the acute asthmaticcondition by altering the IL-10-producing lymphocyte population. The current resultshave potential importance for understanding the mechanistic aspects of function ofestrogen in allergic inflammatory response.