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| DC 欄位 | 值 | 語言 |
|---|---|---|
| dc.contributor.advisor | 張永祺(Yung-Chi Chang) | |
| dc.contributor.author | Tzu-Ching Lan | en |
| dc.contributor.author | 藍子晴 | zh_TW |
| dc.date.accessioned | 2022-11-25T03:03:31Z | - |
| dc.date.available | 2026-08-24 | |
| dc.date.copyright | 2021-09-16 | |
| dc.date.issued | 2021 | |
| dc.date.submitted | 2021-08-24 | |
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| dc.identifier.uri | http://tdr.lib.ntu.edu.tw/jspui/handle/123456789/81783 | - |
| dc.description.abstract | Sialic acid-binding immunoglobulin-like lectin (Siglec)是一種廣泛表現在不同免疫細胞表面的受體，可辨識不同病原體，並引起相對應免疫反應，其中Siglec-5和Siglec-14均可表現於人類單核球細胞，且他們因可辨識相同配體，但傳遞相反訊號，因此被稱為「成對受體」。過去發現在細菌感染時，表現SIGLEC14 allele的個體會有較明顯的發炎反應，在我們的實驗中亦發現，穩定表現Siglec-14的THP-1 (S14/THP-1)受病毒感染後，也會產生較多的促炎性細胞激素，但與抗病毒反應有關的IFN-β表現卻較低。為了解Siglec是透過何種分子機制，調控了THP-1細胞的免疫反應，我們首先利用NanoString nCounter Human Immunology Panel分析當S5/THP-1、S14/THP-1受病毒感染後，細胞內免疫相關基因之表現量的改變。接著我們逐一分析與病毒感染導致之發炎反應相關的訊息傳遞路徑，我們發現與S5/ THP-1相比，S14/THP-1內ERK/ RSK1/ p65路徑及SYK，均有較活化的情形。而在與調控IFN-β表現相關的路徑中，雖然S5/THP-1和S14/THP-1在TBK1及IRF3的活化情況並無顯著差異，但我們發現在S14/ THP-1中，GSK3β的活化受到抑制，且β-catenin在細胞內有較明顯累積的情形，可能因此抑制了IRF3對IFN-β的轉錄活性。總結實驗結果，我們初步發現在病毒感染時，成對受體Siglec-5和Siglec-14對免疫反應之分子機制的調控作用。 | zh_TW |
| dc.description.provenance | Made available in DSpace on 2022-11-25T03:03:31Z (GMT). No. of bitstreams: 1 U0001-2008202110370900.pdf: 2899766 bytes, checksum: e1d0d9a9d4c0c3d9b225dc85d4c149f0 (MD5) Previous issue date: 2021 | en |
| dc.description.tableofcontents | 口試委員審定書 i 致謝 ii 中文摘要 iii Abstract iv 目錄 vi 壹、 研究背景與動機 1 一、 單核球細胞與模式辨認受體 1 二、 Sialic acid-binding immunoglobulin-like lectin (Siglec) 2 三、 成對受體Siglec-5和Siglec-14之基因多型性 2 四、 流行性感冒病毒與仙台病毒 3 1. 流行性感冒病毒 (Influenza virus) 3 2. 仙台病毒 (Sendai virus，SeV) 4 五、 研究動機 5 貳、 實驗材料與研究方法 7 一、 實驗材料 7 1. 病毒株 (Virus strain) 7 2. 細胞株 (Cell line) 7 3. 人類重組Siglec-Fc嵌合蛋白 8 4. 引子 (Primer) 8 5. 酵素免疫分析法試劑組 (ELISA kit) 9 6. 抗體 (Antibody) 9 二、 研究方法 12 1. 病毒生產及定量 12 2. 西方墨點法 (Western blot) 13 3. 人類重組Siglec-Fc嵌合蛋白生產及純化 14 4. 免疫沉澱試驗 (Immunoprecipitation assay) 15 5. 以酵素免疫分析法原理分析Siglec-Fc嵌合蛋白與病毒之交互作用 15 6. 病毒感染細胞：細胞激素及轉錄因子之mRNA表現 16 7. 病毒感染細胞：細胞激素之蛋白質表現 17 8. 病毒感染細胞：細胞內訊息傳遞蛋白之活化 17 9. 病毒感染細胞：訊息傳遞蛋白進入細胞核之情形 18 參、 研究結果 20 一、 Siglec-5和Siglec-14可藉由辨識病毒表面之唾液酸修飾與病毒結合 20 二、 表現Siglec-14之THP-1細胞受SeV感染後有較多促炎性細胞激素產生 21 三、 表現Siglec-14之THP-1細胞受SeV感染後會產生較少第一型干擾素 22 四、 以NanoString及KEGG分析當THP-1細胞受H5N1感染後之基因變化 22 五、 以NanoString及KEGG分析當THP-1細胞受SeV感染後之基因變化 25 六、 Siglec-14對THP-1細胞受SeV感染後MAPK的活化之調控 26 七、 Siglec-14之表現可促進THP-1細胞受SeV感染後ERK/ RSK1/ p65路徑的活化 27 八、 表現Siglec-14之THP-1細胞受SeV感染後有較明顯之SYK的活化 28 九、 TBK1/ IRF3路徑和STING在受Siglec-14調控之第一型干擾素表現中所扮演的角色 28 十、 轉錄因子BCL6、GFI1、ZBTB16於S5/THP-1和S14/THP-1內之表現具差異 29 十一、 Siglec-14之表現會抑制THP-1細胞受SeV感染後GSK3β的活化及促進β-catenin的累積 30 肆、 討論與未來研究方向 32 參考文獻 38 研究結果圖表 42 附錄 63 | |
| dc.language.iso | zh-TW | |
| dc.subject | 第一型干擾素 | zh_TW |
| dc.subject | Siglecs | zh_TW |
| dc.subject | THP-1 | zh_TW |
| dc.subject | A型流感病毒 | zh_TW |
| dc.subject | 仙台病毒 | zh_TW |
| dc.subject | 先天性免疫反應 | zh_TW |
| dc.subject | 抗病毒免疫反應 | zh_TW |
| dc.subject | 促炎性細胞激素 | zh_TW |
| dc.subject | Siglecs | en |
| dc.subject | type I IFN | en |
| dc.subject | proinflammatory cytokines | en |
| dc.subject | antiviral immune responses | en |
| dc.subject | innate immune responses | en |
| dc.subject | Sendai virus | en |
| dc.subject | influenza A virus | en |
| dc.subject | THP-1 | en |
| dc.title | 探討Siglec-5及Siglec-14受體對單核球細胞之抗病毒免疫反應的調控作用 | zh_TW |
| dc.title | To investigate the role of Siglec-5 and Siglec-14 in the monocyte-mediated antiviral immune response | en |
| dc.date.schoolyear | 109-2 | |
| dc.description.degree | 碩士 | |
| dc.contributor.oralexamcommittee | 楊宏志(Hsin-Tsai Liu),陳念榮(Chih-Yang Tseng) | |
| dc.subject.keyword | Siglecs,THP-1,A型流感病毒,仙台病毒,先天性免疫反應,抗病毒免疫反應,促炎性細胞激素,第一型干擾素, | zh_TW |
| dc.subject.keyword | Siglecs,THP-1,influenza A virus,Sendai virus,innate immune responses,antiviral immune responses,proinflammatory cytokines,type I IFN, | en |
| dc.relation.page | 64 | |
| dc.identifier.doi | 10.6342/NTU202102538 | |
| dc.rights.note | 同意授權(全球公開) | |
| dc.date.accepted | 2021-08-24 | |
| dc.contributor.author-college | 醫學院 | zh_TW |
| dc.contributor.author-dept | 微生物學研究所 | zh_TW |
| dc.date.embargo-lift | 2026-08-24 | - |
| 顯示於系所單位： | 微生物學科所 | |
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