Broncho-Vaxom Attenuates Allergic Airway Inflammation by Restoring GSK3β-Related T Regulatory Cell Insufficiency

Ran Fu,Huabin Li,Yueqi Sun,Mengxia Deng,Hua Zhong,Weiping Wen,Dehong Yu,Xianping Zeng,Jian Li,Gobardhan Das

doi:10.1371/journal.pone.0092912

Ran Fu, Huabin Li + Show 8 more

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https://doi.org/10.1371/journal.pone.0092912

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Abstract

BackgroundOral 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.MethodAsthmatic 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.ResultsWe 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.ConclusionOur 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.

Highlights

Allergic airway inflammation such as allergic rhinitis and asthma is characterized by skewed Th2 response, allergen-specific IgE-mediated eosinophilic inflammation, mucus hypersecretion and airway hyperresponsiveness [1]
Our findings provide evidence that oral administration of BV is capable of attenuating airway inflammation in asthmatic mice models, which may be associated with GSK3b-related expansion of Treg cells
These authors contributed to this work

Summary

Introduction

Allergic airway inflammation such as allergic rhinitis and asthma is characterized by skewed Th2 response, allergen-specific IgE-mediated eosinophilic inflammation, mucus hypersecretion and airway hyperresponsiveness [1]. Some studies suggest the insufficient suppression of Treg cells, which may account for the excessive Th2 response in asthma, plays a critical role in initiating allergic sensitization and driving airway hyperresponsiveness [2,3]. Inducing Treg cells through oral administration of bacterial extracts to attenuate the established Th2 response may represent a promising treatment option for allergic rhinitis and asthma. Probiotics treatment through the gastrointestinal mucosa has been shown to attenuate systemic as well as local immunoinflammatory functions [9] This protective effect is thought to be associated with the regulation of common mucosal immune system including lymphoid cells that ‘‘programmed’’ in the gut and subsequently home to other mucosal sites to modulate local inflammatory response. This study sought to assess the effects of oral administration of BV on GSK-3b expression and Treg cells in ovalbumin (OVA)-induced asthmatic mice models

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