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γ-Secretase Inhibitor Alleviates Acute Airway Inflammation of Allergic Asthma in Mice by Downregulating Th17 Cell Differentiation

T helper 17 (Th17) cells play an important role in the pathogenesis of allergic asthma. Th17 cell differentiation requires Notch signaling. γ-Secretase inhibitor (GSI) blocks Notch signaling; thus, it may be considered as a potential treatment for allergic asthma. The aim of this study was to evalua...

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Detalles Bibliográficos
Autores principales: Zhang, Weixi, Zhang, Xueya, Sheng, Anqun, Weng, Cuiye, Zhu, Tingting, Zhao, Wei, Li, Changchong
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Hindawi Publishing Corporation 2015
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4539120/
https://www.ncbi.nlm.nih.gov/pubmed/26339131
http://dx.doi.org/10.1155/2015/258168
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author Zhang, Weixi
Zhang, Xueya
Sheng, Anqun
Weng, Cuiye
Zhu, Tingting
Zhao, Wei
Li, Changchong
author_facet Zhang, Weixi
Zhang, Xueya
Sheng, Anqun
Weng, Cuiye
Zhu, Tingting
Zhao, Wei
Li, Changchong
author_sort Zhang, Weixi
collection PubMed
description T helper 17 (Th17) cells play an important role in the pathogenesis of allergic asthma. Th17 cell differentiation requires Notch signaling. γ-Secretase inhibitor (GSI) blocks Notch signaling; thus, it may be considered as a potential treatment for allergic asthma. The aim of this study was to evaluate the effect of GSI on Th17 cell differentiation in a mouse model of allergic asthma. OVA was used to induce mouse asthma model in the presence and absence of GSI. GSI ameliorated the development of OVA-induced asthma, including suppressing airway inflammation responses and reducing the severity of clinical signs. GSI also significantly suppressed Th17-cell responses in spleen and reduced IL-17 levels in serum. These findings suggest that GSI directly regulates Th17 responses through a Notch signaling-dependent pathway in mouse model of allergic asthma, supporting the notion that GSI is a potential therapeutic agent for the treatment of allergic asthma.
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spelling pubmed-45391202015-09-03 γ-Secretase Inhibitor Alleviates Acute Airway Inflammation of Allergic Asthma in Mice by Downregulating Th17 Cell Differentiation Zhang, Weixi Zhang, Xueya Sheng, Anqun Weng, Cuiye Zhu, Tingting Zhao, Wei Li, Changchong Mediators Inflamm Research Article T helper 17 (Th17) cells play an important role in the pathogenesis of allergic asthma. Th17 cell differentiation requires Notch signaling. γ-Secretase inhibitor (GSI) blocks Notch signaling; thus, it may be considered as a potential treatment for allergic asthma. The aim of this study was to evaluate the effect of GSI on Th17 cell differentiation in a mouse model of allergic asthma. OVA was used to induce mouse asthma model in the presence and absence of GSI. GSI ameliorated the development of OVA-induced asthma, including suppressing airway inflammation responses and reducing the severity of clinical signs. GSI also significantly suppressed Th17-cell responses in spleen and reduced IL-17 levels in serum. These findings suggest that GSI directly regulates Th17 responses through a Notch signaling-dependent pathway in mouse model of allergic asthma, supporting the notion that GSI is a potential therapeutic agent for the treatment of allergic asthma. Hindawi Publishing Corporation 2015 2015-08-03 /pmc/articles/PMC4539120/ /pubmed/26339131 http://dx.doi.org/10.1155/2015/258168 Text en Copyright © 2015 Weixi Zhang et al. https://creativecommons.org/licenses/by/3.0/ This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
spellingShingle Research Article
Zhang, Weixi
Zhang, Xueya
Sheng, Anqun
Weng, Cuiye
Zhu, Tingting
Zhao, Wei
Li, Changchong
γ-Secretase Inhibitor Alleviates Acute Airway Inflammation of Allergic Asthma in Mice by Downregulating Th17 Cell Differentiation
title γ-Secretase Inhibitor Alleviates Acute Airway Inflammation of Allergic Asthma in Mice by Downregulating Th17 Cell Differentiation
title_full γ-Secretase Inhibitor Alleviates Acute Airway Inflammation of Allergic Asthma in Mice by Downregulating Th17 Cell Differentiation
title_fullStr γ-Secretase Inhibitor Alleviates Acute Airway Inflammation of Allergic Asthma in Mice by Downregulating Th17 Cell Differentiation
title_full_unstemmed γ-Secretase Inhibitor Alleviates Acute Airway Inflammation of Allergic Asthma in Mice by Downregulating Th17 Cell Differentiation
title_short γ-Secretase Inhibitor Alleviates Acute Airway Inflammation of Allergic Asthma in Mice by Downregulating Th17 Cell Differentiation
title_sort γ-secretase inhibitor alleviates acute airway inflammation of allergic asthma in mice by downregulating th17 cell differentiation
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4539120/
https://www.ncbi.nlm.nih.gov/pubmed/26339131
http://dx.doi.org/10.1155/2015/258168
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