지원사업
학술연구/단체지원/교육 등 연구자 활동을 지속하도록 DBpia가 지원하고 있어요.
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논문 기본 정보
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- 학위논문
- 저자정보
- 지도교수
- 김영미
- 발행연도
- 2013
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초록· 키워드
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Allergic diseases have increased rapidly over the past decades, affecting an estimated 20∼30% of the population in developed countries. Also, the Korea National Statistical Ministry of Health and Welfare Service has reported that patients of children and adolescents with allergic diseases are increasing these days.
Immune system plays a role in protecting the human body from extraneous foreign substance. However, in the case of hypersensitivity reaction, immune system does not protect the body against innocuous environmental proteins (antigens, Ag), but rather to attack, that cause allergic diseases. In IgE-mediated allergic reaction process, mast cells have pivotal role to induce allergic response. Binding of Ag to the high affinity IgE receptors (FcεRI) which located on the surface of mast cells, triggers mast cell activation and subsequently induces the release of preformed intragranular mediators (histamine, arachidonic acid metabolites, proteases, serotonin, and heparin etc), and eventually allergic reaction occur. Thus, it is important to investigate FcεRI mediated signalling pathway for treat allergic diseases.
In this study, we used a typical costal sand dune plant, Carex pumila which was frequently emerges in the coast of South Korea. We investigated how Carex pumila extract (CPE) suppresses mast cell activation and IgE-mediated allergic response in vivo and in vitro. As the resutls, CPE inhibited antigen-stimulated degranulation in RBL-2H3 cells, BMMCs and IgE-mediated passive cutaneous anaphylaxis (PCA) in mice. CPE also suppresssed the expression of pro-inflammatory cytokines TNF-α and IL-4 in RBL-2H3 cells. As its mechanism of action, CPE suppressed the activation of Syk, a pivotal signal molecule in FcεRI-mediated signalling pathway, and that of LAT, a downstream adaptor molecule of Syk, in a dose-dependent manner. Also CPE suppressed activation of mitogen-activated protein (MAP) Kinase family, p38, ERK1/2, JNK, and Akt. Altogether, CPE inhibited mast cell activation and IgE-meidated allergic resposne by antigen through suppressing the activation of Syk. These results suggest that CPE may be useful for the treatment of allergic diseases.
Immune system plays a role in protecting the human body from extraneous foreign substance. However, in the case of hypersensitivity reaction, immune system does not protect the body against innocuous environmental proteins (antigens, Ag), but rather to attack, that cause allergic diseases. In IgE-mediated allergic reaction process, mast cells have pivotal role to induce allergic response. Binding of Ag to the high affinity IgE receptors (FcεRI) which located on the surface of mast cells, triggers mast cell activation and subsequently induces the release of preformed intragranular mediators (histamine, arachidonic acid metabolites, proteases, serotonin, and heparin etc), and eventually allergic reaction occur. Thus, it is important to investigate FcεRI mediated signalling pathway for treat allergic diseases.
In this study, we used a typical costal sand dune plant, Carex pumila which was frequently emerges in the coast of South Korea. We investigated how Carex pumila extract (CPE) suppresses mast cell activation and IgE-mediated allergic response in vivo and in vitro. As the resutls, CPE inhibited antigen-stimulated degranulation in RBL-2H3 cells, BMMCs and IgE-mediated passive cutaneous anaphylaxis (PCA) in mice. CPE also suppresssed the expression of pro-inflammatory cytokines TNF-α and IL-4 in RBL-2H3 cells. As its mechanism of action, CPE suppressed the activation of Syk, a pivotal signal molecule in FcεRI-mediated signalling pathway, and that of LAT, a downstream adaptor molecule of Syk, in a dose-dependent manner. Also CPE suppressed activation of mitogen-activated protein (MAP) Kinase family, p38, ERK1/2, JNK, and Akt. Altogether, CPE inhibited mast cell activation and IgE-meidated allergic resposne by antigen through suppressing the activation of Syk. These results suggest that CPE may be useful for the treatment of allergic diseases.
목차
국문요약 ················································································································ⅠList of Figures ·································································································· ⅢList of Tables ···································································································· ⅣⅠ. 서 론 ········································································································ 1Ⅱ. 실험재료 및 실험방법 ················································································ 121. 실험재료 ····································································································· 122. β-hexosaminidase 측정 ········································································ 143. RT-PCR(Reverse Transcriptase-Polymerase Chain Reaction) ········ 154. Immunoblot analysis ·············································································· 165. Passive cutaneous anaphylaxis(PCA) ············································· 176. Histological analysis ············································································· 187. 통계학적 분석 ····························································································· 18Ⅲ. 실험 결과 ······································································································ 191. CPE의 항원자극으로 유발된 비만세포 탈과립의 억제 효과 ········· 192. CPE 처리 시 RBL-2H3세포에서 항원에 의해 유도된 TNF-α, IL-4expression 억제 효과 ······················································································ 223. CPE의 ionomycin과 thapsigargin으로 유도된 RBL-2H3세포의 탈과립에 대한 억제 효과 ······················································································· 244. CPE 처리 시 RBL-2H3 cells과 BMMCs에서의 Syk 및 하위 신호전달 단백질들의 인산화 억제 효과 ································································· 265. In vivo 상에서의 CPE의 알레르기 억제 효과 ·································· 28Ⅳ. 고 찰 ······································································································ 30Ⅴ. 참고 문헌 ······································································································ 33Abstract ··············································································································· 40
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