2013 Fiscal Year Final Research Report
Eosinophil-epithelial cell interactions stimulate the production of MUC5AC mucin and profibrotic cytokines involved in airway tissue remodeling
| Project/Area Number |
23592509
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Multi-year Fund |
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| Section | 一般 |
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| Research Field |
Otorhinolaryngology
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| Research Institution | Shiga University of Medical Science |
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Principal Investigator |
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| Co-Investigator(Kenkyū-buntansha) |
KOUZAKI Hideaki 滋賀医科大学, 医学部, 講師 (10402710)
KOUZAKI Hideaki 滋賀医科大学, 医学部, 医員 (50505592)
OGAWA Takao 滋賀医科大学, 医学部, 助教 (90549908)
TOJIMA Ichiro 滋賀医科大学, 医学部, 助教 (80567347)
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| Project Period (FY) |
2011 – 2013
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| Keywords | 好酸球 / 鼻副鼻腔炎 / 粘液産生 / 鼻茸 / 上皮細胞 / 組織リモデリング / ＥＧＦ受容体 / MUC5AC |
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| Research Abstract |
To elucidate the role of eosinophils in tissue remodeling of chronic rhinosinusitis, eosinophil-epithelial interactions were examined by the co-culture of airway epithelial (NCI-H292) cells with the eosinophilic cell line EoL-1 or with human blood eosinophils.
Eosinophil-epithelial interactions stimulated the secretion of MUC5AC, PDGF, VEGF, TGF-beta and IL-8 in culture supernatants. The EGFR tyrosine kinase inhibitor AG1478 inhibited the co-culture-induced secretion of MUC5AC, PDGF, VEGF, and IL-8. Neutralizing antibodies directed against TGF-alpha or amphiregulin and pan-metalloprotease inhibitor GM6001 inhibited the co-culture-induced secretion of MUC5AC and amphiregulin from the co-cultured NCI-H292 cells. These results indicate that eosinophil-epithelial interactions stimulate tissue remodeling induced by MUC5AC mucin, PDGF and VEGF, probably mediated by metalloprotease-dependent EGFR transactivation via amphiregulin and TGF-alpha released from the epithelial cells.
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