751. Inhibition effect of blunting Notch signaling on food allergy through improving T H 1/T H 2 balance in mice.
- Author
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Jiang S, Han S, Chen J, Li X, and Che H
- Subjects
- Animals, Biomarkers, Capillary Permeability, Cell Degranulation immunology, Cytokines metabolism, Disease Models, Animal, Female, GATA3 Transcription Factor genetics, GATA3 Transcription Factor metabolism, Gene Expression, Immunoglobulin Isotypes blood, Immunoglobulin Isotypes immunology, Lymphocyte Count, Mast Cells immunology, Mast Cells metabolism, Mice, Peptides pharmacology, Quinolines pharmacology, Food Hypersensitivity immunology, Food Hypersensitivity metabolism, Receptors, Notch metabolism, Signal Transduction, Th1 Cells immunology, Th1 Cells metabolism, Th1-Th2 Balance, Th2 Cells immunology, Th2 Cells metabolism
- Abstract
Background: Notch signaling regulates proliferation, differentiation, and function of dendritic cells, T cells, and mast cells, as well as many other immune cells, which act as important parts in food allergy, Notch signaling may play an important role in food allergy., Objective: To investigate the role of Notch signaling in IgE-mediated food allergy., Methods: An ovalbumin-induced food allergy mouse model was built (cholera toxin as adjuvant) and Notch signaling was blunted by FLI-06 and MW167, which inhibited Notch receptor-expressing phase and the γ-secretase-affecting phase, respectively. Then food allergy indicators, including levels of serum antibodies, cytokines, and degranulation, were examined. Meanwhile, clinical features, such as vascular permeability changes, intestinal permeability changes, body temperature changes, and symptoms, were also observed., Results: After blunting Notch signaling, the levels of serum ovalbumin specific IgE and IgG
1 were decreased significantly, suggesting that blunting Notch signaling inhibited antibody responses. The levels of TH 1 cytokines (interferon-γ) were increased significantly, whereas the levels of TH 2 cytokines (interleukin-4, -5, and -13) were decreased significantly, suggesting TH 2 polarization was suppressed after blunting Notch signaling. The expression of T-bet was significantly increased, whereas the expression of Gata-3 was significantly reduced in both messenger RNA and protein levels, indicating TH 2 polarization was inhibited and TH 1 polarization was enhanced after blunting Notch signaling. Moreover, allergic clinical features of mice were alleviated after blunting Notch signaling., Conclusion: Food allergy was inhibited by blunting Notch signaling through suppressing TH 2 polarization, enhancing TH 1 cell differentiation and promoting TH 1/TH 2 balance in mice. Notch signaling plays a key role in IgE-mediated food allergy., (Copyright © 2016 American College of Allergy, Asthma & Immunology. Published by Elsevier Inc. All rights reserved.)- Published
- 2017
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