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支气管疫苗通过恢复 GSK3β 相关 T 调节细胞不足来减轻过敏性气道炎症。

Broncho-Vaxom attenuates allergic airway inflammation by restoring GSK3β-related T regulatory cell insufficiency.

机构信息

Allergy and Cancer Center, Otorhinolarygology Hospital, The First Affiliated Hospital of Sun Yat-sen University, Guangzhou, China.

Department of Otolaryngology, Head and Neck Surgery, Xinhua Hospital, Shanghai Jiaotong University School of Medicine, Shanghai, China.

出版信息

PLoS One. 2014 Mar 25;9(3):e92912. doi: 10.1371/journal.pone.0092912. eCollection 2014.

Abstract

BACKGROUND

Oral administration of bacterial extracts (eg, Broncho-Vaxom (BV)) has been proposed to attenuate asthma through modulating Treg cells. However, the underlying mechanism has not been fully characterized. This study sought to assess the effects of oral administration of BV on GSK-3β expression and Treg cells in ovalbumin (OVA)-induced asthmatic mice models.

METHOD

Asthmatic mice models were established with OVA challenge and treated with oral administration of BV. Next, infiltration of inflammatory cells including eosinophil and neutrophils, mucous metaplasia, levels of Th1/Th2/Treg-typed cytokines and expression of GSK3β and Foxp3 were examined in asthmatic mice models by histological analysis, Bio-Plex and western blot, respectively. Moreover, the frequencies of Treg cells were evaluated in cultured splenocytes by flow cytometry in the presence of BV or GSK3β siRNA interference.

RESULTS

We found significant decrease of infiltrated inflammatory cells in bronchoalveolar lavage fluid (BALF) in asthmatic mice models after oral administration of BV. Oral administration of BV was shown to significantly suppress mucus metaplasia, Th2-typed cytokine levels and GSK3β expression while increasing Foxp3 production in asthmatic mice models. Moreover, BV significantly enhanced GSK3β-related expansion of Treg cells in cultured spleen cells in vitro.

CONCLUSION

Our findings provide evidence that oral administration of BV is capable of attenuating airway inflammation in asthmatic mice models, which may be associated with GSK3β-related expansion of Treg cells.

摘要

背景

口服细菌提取物(如 Broncho-Vaxom(BV))已被提议通过调节 Treg 细胞来减轻哮喘。然而,其潜在机制尚未完全阐明。本研究旨在评估口服 BV 对卵清蛋白(OVA)诱导的哮喘小鼠模型中 GSK-3β 表达和 Treg 细胞的影响。

方法

通过 OVA 激发建立哮喘小鼠模型,并进行口服 BV 治疗。然后,通过组织学分析、Bio-Plex 和 Western blot 分别检测哮喘小鼠模型中炎症细胞(包括嗜酸性粒细胞和中性粒细胞)浸润、黏液化生、Th1/Th2/Treg 细胞因子水平以及 GSK3β 和 Foxp3 的表达。此外,通过流式细胞术在存在 BV 或 GSK3β siRNA 干扰的情况下评估培养的脾细胞中 Treg 细胞的频率。

结果

我们发现,口服 BV 后,哮喘小鼠模型的支气管肺泡灌洗液(BALF)中浸润的炎症细胞明显减少。BV 口服给药可显著抑制哮喘小鼠模型中的黏液化生、Th2 细胞因子水平和 GSK3β 表达,同时增加 Foxp3 的产生。此外,BV 还能显著增强体外培养脾细胞中 GSK3β 相关的 Treg 细胞扩增。

结论

我们的研究结果提供了证据表明,口服 BV 能够减轻哮喘小鼠模型中的气道炎症,这可能与 GSK3β 相关的 Treg 细胞扩增有关。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7c4d/3965496/e4f3a8119c3b/pone.0092912.g001.jpg

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