Epithelial cells expressed IL-33 to promote degranulation of mast cells through inhibition on ST2/PI3K/mTOR-mediated autophagy in allergic rhinitis.
Cell Cycle
; 19(10): 1132-1142, 2020 05.
Article
em En
| MEDLINE
| ID: mdl-32298206
ABSTRACT
Nasal epithelial cells are the first barrier against allergen infiltration in allergic rhinitis (AR), and the relationship between nasal epithelial cells and mast cell-mediated hypersensitivity remains unclear. This study aimed to investigate the possible association between allergen-challenged nasal epithelial cells (AR-HNEpC) and mast cell degranulation in AR. Our data revealed that calcium influx and degranulation were increased in AR-HNEpC-co-cultured mast cells. Expression of IL-33, a factor that binds to ST2 receptors on mast cells and regulates their degranulation, was elevated in AR-HNEpC. Blocking IL-33/ST2 pathway activated autophagy and inhibited degranulation and inflammatory factor release in mast cells. Furthermore, PI3K/mTOR was increased in IL-33-treated mast cells. Inhibition on PI3K/mTOR pathway enhanced autophagy and inhibited degranulation. Analysis using an in vivo AR model supported the above findings. In conclusion, IL-33 from epithelial cells promotes degranulation of mast cells in AR through inhibition on ST2/PI3K/mTOR-mediated autophagy, which provides a potential therapeutic target for the disease.Abbreviations AR allergic rhinitis; IL interleukin; TNF-α tumor necrosis factor-alpha; INF-γ interferon-gamma; HNEpC human nasal epithelial cell line; ATCC American Type Culture Collection; C48/80 compound 48/80; 3-MA 3-methyladenine; qPCR quantitative PCR; AR-HNEpC dust mite allergen-treated nasal epithelial cells; IgE immunoglobulin E; Atg7 autophagy-related gene 7.
Palavras-chave
Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
Autofagia
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Degranulação Celular
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Fosfatidilinositol 3-Quinases
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Células Epiteliais
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Serina-Treonina Quinases TOR
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Rinite Alérgica
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Interleucina-33
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Proteína 1 Semelhante a Receptor de Interleucina-1
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Mastócitos
Tipo de estudo:
Prognostic_studies
Limite:
Animals
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Humans
Idioma:
En
Ano de publicação:
2020
Tipo de documento:
Article