Kim Boo-Young, Park Hyang Rim, Shin Ji-Hyeon, Kim Sung Won, Kim Soo Whan
Department of Otolaryngology-Head and Neck Surgery, The Catholic University of Korea, College of Medicine, Seoul, Korea.
Laryngoscope. 2014 Oct;124(10):E399-404. doi: 10.1002/lary.24714. Epub 2014 Jun 3.
OBJECTIVES/HYPOTHESIS: In this study, we addressed the immunotherapeutic potential of human placental extract (HPE) in a murine allergic rhinitis (AR) model and explored its immunological mechanisms.
In vivo study using an animal model.
HPE was administered to BALB/c mice before sensitization with allergen (Dermatophagoides farinae [Derf]) (pre-S group) or after allergen challenge (post-C group). The groups were compared with Derf-treated mice that received no HPE (Derf group) and phosphate buffered saline (PBS)-treated mice (control). Allergic symptom scores, eosinophil counts, and serum Derf-specific IgE levels were measured. mRNA expression levels of interferon (IFN)-γ, T-bet, interleukin (IL)-4, GATA-3, and Foxp3 in nasal mucosa were determined by real-time polymerase chain reaction. IFN-γ, T-bet, IL-4, and GATA-3 were confirmed by Western blotting analysis. Spleen CD4(+) CD25(+) Foxp3(+) T cells were detected using flow cytometry.
Rubbing motions, serum Derf-specific IgE, GATA-3 mRNA levels, IL-4 mRNA levels, and tissue eosinophil counts were decreased in both pre-S and post-C groups (all P < 0.05). Western blots showed decreased expression of GATA-3 and IL-4 in both pre-S and post-C groups as compared to the Derf group. An increased percentage of CD4(+) CD25(+) Foxp3(+) T cells and an increased level of Foxp3 mRNA were found in pre-S and post-C groups as compared to those in the Derf group (all P < 0.05).
Both prophylactic and therapeutic treatments with HPE significantly reduced allergic inflammation in nasal mucosa and had the potential to induce regulatory T cells in a murine model of AR.
目的/假设:在本研究中,我们探讨了人胎盘提取物(HPE)在小鼠变应性鼻炎(AR)模型中的免疫治疗潜力,并探究其免疫机制。
使用动物模型进行的体内研究。
在致敏原(粉尘螨 [Derf])致敏前(致敏前组)或致敏原激发后(激发后组),对BALB/c小鼠给予HPE。将这些组与未接受HPE的Derf处理小鼠(Derf组)和磷酸盐缓冲盐水(PBS)处理小鼠(对照组)进行比较。测量变应性症状评分、嗜酸性粒细胞计数和血清Derf特异性IgE水平。通过实时聚合酶链反应测定鼻黏膜中干扰素(IFN)-γ、T-bet、白细胞介素(IL)-4、GATA-3和Foxp3的mRNA表达水平。通过蛋白质印迹分析确认IFN-γ、T-bet、IL-4和GATA-3。使用流式细胞术检测脾脏CD4(+) CD25(+) Foxp3(+) T细胞。
致敏前组和激发后组的搔抓动作、血清Derf特异性IgE、GATA-3 mRNA水平、IL-4 mRNA水平和组织嗜酸性粒细胞计数均降低(均P < 0.05)。蛋白质印迹显示,与Derf组相比,致敏前组和激发后组中GATA-3和IL-4的表达均降低。与Derf组相比,致敏前组和激发后组中CD4(+) CD25(+) Foxp3(+) T细胞的百分比增加,Foxp3 mRNA水平升高(均P < 0.05)。
在AR小鼠模型中,HPE的预防性和治疗性治疗均显著减轻了鼻黏膜的变应性炎症,并具有诱导调节性T细胞的潜力。