호산구성 비부비동염의 비용 형성에서 interleukin-17A의 역할

Abstract

학위논문 (박사)-- 서울대학교 대학원 : 의학과 면역학전공, 2015. 8. 이재서.Background: Nasal polyposis associated with chronic rhinosinusitis (CRS) is a chronic inflammatory disease which is characterized by infiltration of many inflammatory cells. Meanwhile, interleukin (IL)-17A is a well-known proinflammatory cytokine which induces both eosinophilic and neutrophilic inflammation. We investigated the role of IL-17A in the development of nasal polyps in the CRS murine model. Materials & Methods: Eosinophilic CRS with nasal polyps was induced by using ovalbumin (OVA) and Staphylococcus aureus enterotoxin B (SEB) in wild-type BALB/c and IL-17A knock-out (KO) mice. Histopathologic changes of the sinonasal cavity were evaluated using hematoxylin and eosin, Periodic acid-Schiff, Sirius red, Masson’s trichrome and immunohistochemistry. The levels of cytokines in splenocyte supernatants and total and OVA-specific IgEs in sera were measured using enzyme-linked immunosorbent assay. The expression levels of cytokines in the nasal mucosa were assessed by quantitative real-time polymerase chain reaction. Results: Under the IL-17A deficiency, cytokines (IL-4, IL-5 and interferon-γ) in splenocyte supernatants as well as total and OVA-specific IgEs in sera were reduced significantly. Infiltration of both eosinophils and neutrophils into the nasal mucosa, subepithelial fibrosis and goblet cell count also decreased significantly in IL-17A KO mice treated with both OVA and SEB compared with those in the wild-type counterpart. However, there were no significant differences in either numbers or sizes of polypoid lesions among groups. Meanwhile, IL-4 increased and interferon-γ decreased in the nasal mucosa in IL-17A KO mice treated with both OVA and SEB. Conclusions: This study suggests that even though IL-17A plays an important role in both local inflammation and remodeling of the nasal mucosa in CRS, it cannot entirely account for the development of nasal polyps.Abstract ----------------------------------------------- i Contents --------------------------------------------- iv List of Tables ----------------------------------------- v List of Figures ---------------------------------------- vi List of Abbreviations --------------------------------- viii Introduction ------------------------------------------- 1 Materials and Methods -------------------------------- 3 Results ---------------------------------------------- 10 Discussion ------------------------------------------ 14 References ------------------------------------------ 21 Tables ---------------------------------------------- 28 Figures ---------------------------------------------- 29 Abstract (Korean) ------------------------------------ 40Docto