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Mediators Inflamm. 2015;2015:258168. doi: 10.1155/2015/258168. Epub 2015 Aug 3.

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

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Department of Pediatric Pulmonology, The Second Affiliated Hospital & Yuying Children's Hospital of Wenzhou Medical University, 109 Xueyuan Road, Wenzhou, Zhejiang 325027, China.
Division of Allergy and Immunology, Department of Pediatrics, Virginia Commonwealth University, P.O. Box 980225, Richmond, VA 23298, USA.


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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