目的:G蛋白偶联雌激素受体(GPER)是位于质膜上的雌激素受体。我们之前报道了GPER特异性激动剂G-1的给药,在小鼠模型中抑制急性卵清蛋白(OVA)诱导的哮喘的发展。在这里,我们评估了GPER在慢性OVA哮喘小鼠模型中的作用.
方法:对患有慢性OVA哮喘的BALB/c小鼠皮下给予G-1或生理盐水,并进行病理和免疫学评估。此外,使用流式细胞术测量脾脏中表达Foxp3的CD4阳性T细胞和肺中的ILC2。
结果:我们观察到G-1治疗组的支气管肺泡灌洗液(BALF)中炎性细胞数量显着减少。在气道中,炎性细胞积累,Th2细胞因子(IL-4,IL-5,IL-13和eotaxin)和上皮细胞因子TSLP被抑制,而在BALF,抗炎细胞因子(IL-10和TGF-β)增加。此外,在脾单核细胞中,在G-1组中,表达Foxp3的CD4阳性T细胞增加,而用G-1治疗没有改变ILC2在肺中的百分比。
结论:G-1给药抑制了慢性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。
OBJECTIVE: 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.
CONCLUSIONS: G-1 administration suppressed allergic airway inflammation in mice with chronic OVA asthma. GPER may be a potential therapeutic target for chronic allergic asthma.