Epithelial cells expressed IL-33 to promote degranulation of mast cells through inhibition on ST2/PI3K/mTOR-mediated autophagy in allergic rhinitis
| Autor: | Qiu-Ju Huang, Zhi Fu, Min Zeng, Xin Wei, Jing Zheng, Lian-Ya Zeng, Jia-Bin Nian |
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| Rok vydání: | 2020 |
| Předmět: |
0301 basic medicine
Transfection Immunoglobulin E Cell Degranulation Cell Line Rats Sprague-Dawley Phosphatidylinositol 3-Kinases 03 medical and health sciences 0302 clinical medicine Autophagy medicine Animals Humans Mast Cells Molecular Biology PI3K/AKT/mTOR pathway biology TOR Serine-Threonine Kinases Pyroglyphidae Degranulation Interleukin Epithelial Cells Cell Biology Allergens Interleukin-33 Mast cell Interleukin-1 Receptor-Like 1 Protein Rhinitis Allergic Recombinant Proteins Rats Interleukin 33 Disease Models Animal 030104 developmental biology medicine.anatomical_structure 030220 oncology & carcinogenesis biology.protein Cancer research Tumor necrosis factor alpha Signal Transduction Research Paper Developmental Biology |
| Zdroj: | Cell Cycle |
| ISSN: | 1551-4005 1538-4101 |
| DOI: | 10.1080/15384101.2020.1749402 |
| Popis: | 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 |
| Databáze: | OpenAIRE |
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