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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 reduced production of IL-17. Serum IL-17 levels were measured from sham, OVA, and OVA plus GSI groups using standardized sandwich ELISA. Data expressed here are Mean ± SEM. N = 8. ∗P < 0.01 compared with the sham group. #P < 0.01 compared with the vehicle group.
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fig5: GSI administration reduced production of IL-17. Serum IL-17 levels were measured from sham, OVA, and OVA plus GSI groups using standardized sandwich ELISA. Data expressed here are Mean ± SEM. N = 8. ∗P < 0.01 compared with the sham group. #P < 0.01 compared with the vehicle group.

Mentions: Th17 cells are the main source of IL-17. To further examine the function of such Th17 cells, serum levels of IL-17 were measured from OVA-induced asthma mice. As illustrated in Figure 5, sham group expressed a baseline level of IL-17 in serum at 48.07 ± 5.73 pg/mL. The IL-17 level was significantly elevated in OVA-induced asthma mice (120.09 ± 5.73 pg/mL, P < 0.01). GSI administration during challenge phase significantly reduced the IL-17 level to 81.82 ± 8.95 pg/mL, P < 0.01. These findings confirm the possibility that GSI downregulates IL-17 expression.


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 reduced production of IL-17. Serum IL-17 levels were measured from sham, OVA, and OVA plus GSI groups using standardized sandwich ELISA. Data expressed here are Mean ± SEM. N = 8. ∗P < 0.01 compared with the sham group. #P < 0.01 compared with the vehicle group.
© Copyright Policy - open-access
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC4539120&req=5

fig5: GSI administration reduced production of IL-17. Serum IL-17 levels were measured from sham, OVA, and OVA plus GSI groups using standardized sandwich ELISA. Data expressed here are Mean ± SEM. N = 8. ∗P < 0.01 compared with the sham group. #P < 0.01 compared with the vehicle group.
Mentions: Th17 cells are the main source of IL-17. To further examine the function of such Th17 cells, serum levels of IL-17 were measured from OVA-induced asthma mice. As illustrated in Figure 5, sham group expressed a baseline level of IL-17 in serum at 48.07 ± 5.73 pg/mL. The IL-17 level was significantly elevated in OVA-induced asthma mice (120.09 ± 5.73 pg/mL, P < 0.01). GSI administration during challenge phase significantly reduced the IL-17 level to 81.82 ± 8.95 pg/mL, P < 0.01. These findings confirm the possibility that GSI downregulates IL-17 expression.

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