G-Protein-Coupled Estrogen Receptor Agonist Suppresses Airway Inflammation In Asthmatic Mouse And Its Mechanisms

Objective: This study aims to investigate the effect of G-protein coupled estrogen receptor (GPER) specific agonist G-1 in allergic asthma. Methods: OVA-sensitized BALB/c mice were treated with G-1 by daily subcutaneous injections during an airway challenge phase, followed by histological and biochemical examination. Results: Administration of G-1 attenuated airway hyperresponsiveness, accumulation of inflammatory cells and the levels of Th2 cytokines (IL-5 and IL-13) in BAL fluid. G-1 treatment also decreased serum levels of anti-OVA IgE antibodies. The frequency of splenic Foxp3(+)CD4(+) regulatory T cells and IL-10-producing GPER(+)CD4(+) T cells was significantly increased in G-1-treated mice. Additionally, splenocytes isolated from G-1-treated mice showed greater IL-10 production. Conclusion: These results indicate that extended GPER activation negatively regulates the acute asthmatic condition. The current results have potential importance for understanding the mechanistic aspects of function of estrogen in allergic inflammatory response.