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

Abstract

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.

• Authors: Weixi Zhang, Xueya Zhang, Anqun Sheng, Cuiye Weng, Tingting Zhu, Wei Zhao, Changchong Li
• Journal: Mediators of inflammation (Mediators Inflamm) Vol. 2015 Pg. 258168 ( 2015) ISSN: 1466-1861 [Electronic] United States
• PMID: 26339131 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Enzyme Inhibitors
• Amyloid Precursor Protein Secretases

Topics

• Amyloid Precursor Protein Secretases (antagonists & inhibitors)
• Animals
• Asthma (drug therapy, immunology, metabolism)
• Cell Differentiation (drug effects)
• Enzyme Inhibitors (therapeutic use)
• Inflammation (drug therapy, immunology, metabolism)
• Male
• Mice
• Mice, Inbred BALB C
• Th17 Cells (cytology, drug effects, metabolism)