Background and Aim

G protein-coupled estrogen receptor (GPER) is an estrogen receptor located on the plasma membrane. We previously reported that the administration of G-1, a GPER-specific agonist, suppressed development of acute ovalbumin (OVA)-induced asthma in a mouse model. Herein, we evaluate the involvement of GPER in a mouse model of chronic OVA asthma.

Methods

G-1 or saline was administered subcutaneously to BALB/c mice with chronic OVA asthma, and pathological and immunological evaluation was performed. In addition, Foxp3-expressing CD4-positive T-cells in the spleen and ILC2 in the lungs were measured using flow cytometry.

Results

We observed a significant decrease in the number of inflammatory cells in the bronchoalveolar lavage fluid (BALF) in the G-1 treated group. In the airways, inflammatory cell accumulation, Th2 cytokines (IL-4, IL-5, IL-13, and eotaxin) and epithelial cytokine TSLP were suppressed, while in the BALF, anti-inflammatory cytokines (IL-10 and TGF-β) were increased. Furthermore, in splenic mononuclear cells, Foxp3-expressing CD4-positive T-cells were increased in the G-1 group, whereas treatment with G-1 did not change the percentage of ILC2 in the lungs.

Conclusion

G-1 administration suppressed allergic airway inflammation in mice with chronic OVA asthma. GPER may be a potential therapeutic target for chronic allergic asthma.

中文翻译：

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G蛋白偶联雌激素受体在慢性哮喘发病机制中的作用

背景和目标

G蛋白偶联雌激素受体（GPER）是位于质膜上的雌激素受体。我们之前报道过，在小鼠模型中，给予 GPER 特异性激动剂 G-1 可以抑制急性卵清蛋白 (OVA) 诱发的哮喘的发生。在此，我们评估了 GPER 在慢性 OVA 哮喘小鼠模型中的参与情况。

方法

慢性OVA哮喘BALB/c小鼠皮下注射G-1或生理盐水，进行病理学和免疫学评价。此外，使用流式细胞术测量了脾脏中表达 Foxp3 的 CD4 阳性 T 细胞和肺中的 ILC2。

结果

我们观察到 G-1 治疗组支气管肺泡灌洗液 (BALF) 中炎症细胞的数量显着减少。在气道中，炎症细胞积聚、Th2 细胞因子（IL-4、IL-5、IL-13 和嗜酸粒细胞趋化因子）和上皮细胞因子 TSLP 受到抑制，而在 BALF 中，抗炎细胞因子（IL-10 和 TGF-β）受到抑制。 ) 有所增加。此外，在脾脏单核细胞中，G-1组中表达Foxp3的CD4阳性T细胞增加，而G-1治疗并没有改变肺部ILC2的百分比。

结论

G-1 给药可抑制慢性 OVA 哮喘小鼠的过敏性气道炎症。GPER可能是慢性过敏性哮喘的潜在治疗靶点。