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完整後設資料紀錄
DC 欄位 | 值 | 語言 |
---|---|---|
dc.contributor.advisor | 陳俊任(Chun-Jen Chen) | |
dc.contributor.author | Hsin-Ling Kuo | en |
dc.contributor.author | 郭信麟 | zh_TW |
dc.date.accessioned | 2021-06-13T15:29:57Z | - |
dc.date.available | 2012-07-21 | |
dc.date.copyright | 2008-07-21 | |
dc.date.issued | 2008 | |
dc.date.submitted | 2008-07-15 | |
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dc.identifier.uri | http://tdr.lib.ntu.edu.tw/jspui/handle/123456789/37489 | - |
dc.description.abstract | 在動物實驗中,人們觀察到N-乙醯幾丁寡糖(NACOS)具有免疫刺激、抗腫瘤、抗微生物等活性,然而對於導致這現象的機制並不是相當清楚。在不同聚合度的NACOS中,我們發現只有N-乙醯幾丁六醣(NACOS-6)與N-乙醯幾丁五醣(NACOS-5)具有刺激小鼠腹腔巨噬細胞、RAW264.7小鼠巨噬細胞株以及THP-1人類單核球細胞株產生TNF-a的活性。添加NF-kB與MAPK (JNK, p38, ERK)路徑之專一性抑制劑,可阻斷NACOS引起之巨噬細胞活化。推斷NACOS藉由與一專一性受體之結合,導致MAPK與NF-kB路徑之活化,產生細胞激素。添加核內體(endosome)酸化抑制劑─氯奎寧,並無法阻斷NACOS-6所引起的巨噬細胞活化。推測NACOS-6刺激巨噬細胞活化不需要經由胞吞作用(endocytosis)。添加其他醣類對受體進行競爭性抑制之結果,發現N-乙醯葡萄糖胺與甘露聚醣(mannan)可對NACOS-6之受體產生競爭性抑制,而甘露糖(mannose)不行,推測甘露糖受體(Mannose receptor)不是NACOS之受體,且藉由其他實驗排除了DC-SIGN與TLR-4等受體。NACOS-6可誘導小鼠樹突細胞成熟,並且提升CD86、CD80等表面分子標記之表現。以NACOS-6作為佐劑,以卵清蛋白(ovalbumin, OVA)為抗原對小鼠進行免疫之模式中,發現NACOS-6可有效刺激對OVA具專一性IgG2a與IFN-r等Th1反應之產生,並且可以有效防護黑色素瘤MO5之侵襲。 | zh_TW |
dc.description.abstract | N-acetyl-chitooligosaccharides (NACOS) have been shown to exhibit immunopotentiating, antitumor, and antimicrobial activities in vivo; however, the mechanisms behind those observations have not been fully understood. We found that among NACOS of different degrees of polymerization (n = 1-6), penta-N-acetylchitopentaose (NACOS-5) and hexa-N-acetylchitohexaose (NACOS-6) were able to stimulate mouse peritoneal macrophages, macrophage-like RAW264.7 cells, and human THP-1 monocytic cells to produce TNF- α and IL-1 α. NACOS stimulation induced the phosphorylation of MAP kinases (JNK, p38 and ERK) and nuclear translocation of NF-κB in RAW264.7 cells, and TNF-α production was blocked by inhibitors of JNK, p38, ERK, and NF-κB activation. Added chloroquine to block the endocytosis-dependent pathway did not inhibit the macrophage activation by NACOS. Macrophage activation by NACOS was competitively blocked by the addition of N-acetyl-D-glucosamine, suggesting that NACOS stimulates macrophages through the binding of a specific receptor. The polysaccharide mannan could also block macrophage activation by NACOS; however mannose did not show any inhibitory effect. NACOS were able to induce the maturation of murine bone-marrow-derived dendritic cells in vitro. These findings indicate that NACOS may stimulate macrophages and dendritic cells through the binding of a specific receptor, leading to the activation of NF-κB and MAP kinases, and the production of proinflammatory cytokines. Using NACOS-6 as an adjuvant, immunization with OVA in C57BL/6 mice resulted in production of OVA specific IgG2a and IFN-γ and the protection from MO5 melanoma challenge. | en |
dc.description.provenance | Made available in DSpace on 2021-06-13T15:29:57Z (GMT). No. of bitstreams: 1 ntu-97-R95b47108-1.pdf: 914054 bytes, checksum: bff1006e8f800a97a4fdf68906143a2b (MD5) Previous issue date: 2008 | en |
dc.description.tableofcontents | 謝誌 I
Abstract II 中文摘要 IV Content V Introduction 1 1. Chitin and chitosan 1 2. Immunostimulation activity of chitin, chitosan and their oligosaccharides 3 3. Other biological activities 4 4. mitogen-activated protein kinases (MAPKs) and NF-kB signaling pathways 4 5. Adjuvant function 8 6. Th1 and Th2 responses 10 7. Rationale of the study 11 Specific aims 12 Materials and Methods 13 1. Animals and cells 13 2. MAPK and NF-kB activation 13 3. Cytosolic and nuclear extract separation 14 4. SDS-PAGE and Western blotting 15 5. Phagocytosis assay 15 6. Cytokine production analysis 16 7. Bone marrow-derived dendritic cell (BMDC) generation 17 8. DC maturation analysis 18 9. Luciferase reporter assay 18 10. Mouse Immunization 19 11. Collection of serum, peritoneal macrophages, and splenocytes 20 12. OVA-specific IgG1, and IgG2a assay 21 13. T cell proliferation 22 17. Statistical analysis 22 Results 23 1. In NACOS of different degrees of polymerization, only NACOS-5 and NACOS-6 have immunostimulating activity 23 2. NACOS-6 promotes the phagocytic activity of macrophages 30 3. NACOS induce NF-kB and mitogen-activated protein kinases (MAPKs) pathway activation 30 4. NACOS stimulate macrophages through a specific receptor which is not DC-SIGN, mannose receptor or TLR-4 42 5. NACOS induce DC maturation 50 6. Evaluation of the adjuvant functions of NACOS 51 7. NACOS-6 induced OVA-specific immune response to protect mice from a challenge with tumor cells expressing the OVA protein 57 Discussion 60 Conclusion 64 Reference 65 | |
dc.language.iso | en | |
dc.title | N-乙醯幾丁寡糖之免疫刺激機轉 | zh_TW |
dc.title | Mechanisms of immunostimulation by N-acetyl-chitooligosaccharides | en |
dc.type | Thesis | |
dc.date.schoolyear | 96-2 | |
dc.description.degree | 碩士 | |
dc.contributor.oralexamcommittee | 林璧鳳(Bi-Fong Lin),徐立中(Li-Chung Hsu),許秉寧(Ping-Ning Hsu) | |
dc.subject.keyword | 幾丁寡糖,免疫佐劑, | zh_TW |
dc.subject.keyword | NACOS,adjuvant,MO5, | en |
dc.relation.page | 71 | |
dc.rights.note | 有償授權 | |
dc.date.accepted | 2008-07-16 | |
dc.contributor.author-college | 生命科學院 | zh_TW |
dc.contributor.author-dept | 微生物與生化學研究所 | zh_TW |
顯示於系所單位: | 微生物學科所 |
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