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

Zhang W, Zhang X, Sheng A, Weng C, Zhu T, Zhao W, Li C - Mediators Inflamm. (2015)

Bottom Line: 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.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.

View Article: PubMed Central - PubMed

Affiliation: Department of Pediatric Pulmonology, The Second Affiliated Hospital & Yuying Children's Hospital of Wenzhou Medical University, 109 Xueyuan Road, Wenzhou, Zhejiang 325027, China.

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.

No MeSH data available.


Related in: MedlinePlus

GSI administration resulted in reduced Th17 cell expansion. BALB/C mice were sensitized i.p. with OVA and challenged with OVA in the presence and absence of GSI. Splenic CD4+ T cells were isolated by magnetic cell sorting. Th17 cells were examined by IL-17A staining and data were analyzed by flow cytometry. Dot plots show as percent of cells positive for CD4 and IL-17A staining. Graphs representative of one of eight experiments.
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fig4: GSI administration resulted in reduced Th17 cell expansion. BALB/C mice were sensitized i.p. with OVA and challenged with OVA in the presence and absence of GSI. Splenic CD4+ T cells were isolated by magnetic cell sorting. Th17 cells were examined by IL-17A staining and data were analyzed by flow cytometry. Dot plots show as percent of cells positive for CD4 and IL-17A staining. Graphs representative of one of eight experiments.

Mentions: To evaluate the effect of GSI treatment on Th17 cell expansion, splenic CD4+ T cells were isolated by magnetic cell sorting. Th17 cells were identified by IL-17A staining. Sham group expressed a baseline Th17 cell frequency of 0.30 ± 0.16% of total splenic CD4+ T cells. OVA-induced asthma mice revealed a significant increase of Th17 cells (2.43 ± 0.69%, P < 0.01, comparing to sham group). GSI treatment reduced Th17 cell frequency to 1.26 ± 0.85% which is statistically significant from OVA group (P < 0.05, Figure 4). This finding indicates that GSI reduces the development of Th17 cells.


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

Zhang W, Zhang X, Sheng A, Weng C, Zhu T, Zhao W, Li C - Mediators Inflamm. (2015)

GSI administration resulted in reduced Th17 cell expansion. BALB/C mice were sensitized i.p. with OVA and challenged with OVA in the presence and absence of GSI. Splenic CD4+ T cells were isolated by magnetic cell sorting. Th17 cells were examined by IL-17A staining and data were analyzed by flow cytometry. Dot plots show as percent of cells positive for CD4 and IL-17A staining. Graphs representative of one of eight experiments.
© Copyright Policy - open-access
Related In: Results  -  Collection

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getmorefigures.php?uid=PMC4539120&req=5

fig4: GSI administration resulted in reduced Th17 cell expansion. BALB/C mice were sensitized i.p. with OVA and challenged with OVA in the presence and absence of GSI. Splenic CD4+ T cells were isolated by magnetic cell sorting. Th17 cells were examined by IL-17A staining and data were analyzed by flow cytometry. Dot plots show as percent of cells positive for CD4 and IL-17A staining. Graphs representative of one of eight experiments.
Mentions: To evaluate the effect of GSI treatment on Th17 cell expansion, splenic CD4+ T cells were isolated by magnetic cell sorting. Th17 cells were identified by IL-17A staining. Sham group expressed a baseline Th17 cell frequency of 0.30 ± 0.16% of total splenic CD4+ T cells. OVA-induced asthma mice revealed a significant increase of Th17 cells (2.43 ± 0.69%, P < 0.01, comparing to sham group). GSI treatment reduced Th17 cell frequency to 1.26 ± 0.85% which is statistically significant from OVA group (P < 0.05, Figure 4). This finding indicates that GSI reduces the development of Th17 cells.

Bottom Line: 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.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.

View Article: PubMed Central - PubMed

Affiliation: Department of Pediatric Pulmonology, The Second Affiliated Hospital & Yuying Children's Hospital of Wenzhou Medical University, 109 Xueyuan Road, Wenzhou, Zhejiang 325027, China.

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.

No MeSH data available.


Related in: MedlinePlus