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  1. NTU Theses and Dissertations Repository
  2. 醫學院
  3. 免疫學研究所
請用此 Handle URI 來引用此文件: http://tdr.lib.ntu.edu.tw/jspui/handle/123456789/49706
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dc.contributor.advisor賴明宗(Ming-Zong Lai)
dc.contributor.authorCheng-Hsun Jaoen
dc.contributor.author饒承訓zh_TW
dc.date.accessioned2021-06-15T11:43:11Z-
dc.date.available2021-08-26
dc.date.copyright2016-08-26
dc.date.issued2016
dc.date.submitted2016-08-15
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dc.identifier.urihttp://tdr.lib.ntu.edu.tw/jspui/handle/123456789/49706-
dc.description.abstract半乳凝集素-3是一種β-半乳糖苷結合凝集素,它對於各種生物功能,例如細胞-細胞相互作用、細胞週期調控、細胞生長、發炎反應和腫瘤發展進程中扮演重要角色。此外,研究也顯示,半乳糖凝集素-3亦可調節各種傳染病和某些特定類型的癌症。然而,半乳凝集素-3在發炎反應中所扮演的角色仍未被釐清。我們使用了骨髓源巨噬細胞來進行研究,探討半乳凝集素-3在脂多醣所誘發的發炎反應中所扮演的角色。結果發現,發炎性細胞激素和發炎小體的前驅物的表現在半乳凝集素-3缺乏的巨噬細胞中有顯著下降的情形。進一步也發現類鐸受體-4下游的信號也較弱。然而,在我們的動物模型所做出來的結果卻認為半乳凝集素-3是一個負向調控者,這個結果暗示著,半乳凝集素-3在不同亞型的巨噬細胞中可能扮演著不同的角色。從我們的實驗結果可以歸納出,內源性半乳凝集素-3在不同類型的巨噬細胞中可能有著不同的功能。未來我們會繼續著重在不同亞型的巨噬細胞,進一步去釐清半乳凝集素-3在發炎小體活化中所扮演的角色,讓我們能更清楚地知道半乳凝集素-3具有怎樣的功能。zh_TW
dc.description.abstractGalectin-3 is a beta-galactoside-binding lectin that participates in orchestrating various biological functions such as cell-cell interaction, cell cycle control, cell growth, inflammation and tumor progression. Also, studies have shown that galectin-3 is involved in the regulation of various infectious diseases and certain type of cancer. Nevertheless, a number of issues related to the role of galectin-3 in inflammation remain to be addressed. Here, we investigated the role of galectin-3 in inflammatory responses triggered by LPS treatment within bone marrow-derived macrophages. As a result, we found that proinflammatory cytokines and precursors of inflammasomes were significantly downregulated in galecitn-3-deficient macrophages. Moreover, TLR4 downstream signaling was impaired. However, our in vivo assay showed that galectin-3 might be a negative regulator. These results imply that galectin-3 might have different functions in different subtypes of macrophage. In summary, our results suggest that endogenous galectin-3 might play distinct roles in various macrophage subtypes. Additional studies are required to elucidate how endogenous galecitn-3 regulates inflammasome activation in different subtypes of macrophages, which it may also help us understand its role in innate immune system.en
dc.description.provenanceMade available in DSpace on 2021-06-15T11:43:11Z (GMT). No. of bitstreams: 1
ntu-105-R03449012-1.pdf: 1387201 bytes, checksum: ae8230beb2071b7fa1506a466b43aa90 (MD5)
Previous issue date: 2016
en
dc.description.tableofcontentsAbstract I
摘要 II
Introduction 1
1. Macrophages – role of macrophages in homeostasis 1
2. Innate immunity 2
2-1. Pattern-recognition receptors (PRRs) 2
2-2. NLRP3 Inflammasomes 3
3. Galectins 7
3-1. Galectin family (β-galactoside binding proteins) 7
3-2. Galectin-3 biology 8
3-3. The function of galectin-3 8
3-4. Crosstalk between galectin-3 and NLRP3 inflammasome 9
Materials and Methods 12
1. Reagents. 12
2. Mice. 12
3. The generation of bone marrow-derived macrophages and ell culture. 13
4. Protein analysis by western blot and ELISA. 13
5. Immunoprecipitation. 15
6. Quantitative PCR. 15
7. Flow cytometry. 16
8. Monosodium urate (MSU)-mediated peritonitis. 16
9. Immunofluorescence assay. 17
10. Statistical analysis. 18
Result 19
1. Comparable macrophage surface marker expression between WT and Gal3-/- BMDMs 19
2. Reduced gene expression levels of TNFα, IL-1β and NLRP3 in Gal3-/- BMDMs. 19
3. Reduced levels of proinflammatory cytokines in Gal3-/- BMDMs. 20
4. Galectin-3 deficiency impairs the level of precursors in NLRP3 inflammasome. 20
5. Galectin-3 is required for TLR4 signaling. 21
6. Interaction of galectin-3 with NLRP3, procaspase-1 and ASC. 22
7. Enhanced MSU-induced peritonitis in Gal3-deficient peritoneal macrophages 22
Discussion 24
Reference 27
Figure contents 36
Figure 1. Comparable macrophage surface marker expression between WT and Gal3-/- BMDMs. 36
Figure 2. Reduced gene expression levels of TNFα, IL-1β and NLRP3 in Gal3-/- BMDMs. 37
Figure 3. Reduced cytokine secretion in Gal3-/- BMDMs. 38
Figure 4. Deficiency of galectin-3 impairs the level of NLRP3 and proIL-1β, leading to reduced IL-1β production. 39
Figure 5. Galectin-3 is required for the NFκB pathway. 40
Figure 7. Increased cytokine secretion in Gal3-/- BMDMs. 42
Figure 8. Interaction between galectin-3 and NLRP3. 43
Appendix - 1 44
Appendix – 2 48
dc.language.isoen
dc.subject巨噬細胞zh_TW
dc.subject半乳糖凝集素-3zh_TW
dc.subjectNLRP3 發炎小體zh_TW
dc.subject類鐸受體-4zh_TW
dc.subjectGalectin-3en
dc.subjectTLR4. macrophagesen
dc.subjectNLRP3 inflammasomeen
dc.title半乳糖凝集素-3在介白素-1β的表現中所扮演的角色zh_TW
dc.titleThe role of Galectin-3 in IL-1β production.en
dc.typeThesis
dc.date.schoolyear104-2
dc.description.degree碩士
dc.contributor.coadvisor劉扶東(Fu-Tong Liu)
dc.contributor.oralexamcommittee伍安怡(Betty Wu-Hsieh)
dc.subject.keyword半乳糖凝集素-3,NLRP3 發炎小體,類鐸受體-4,巨噬細胞,zh_TW
dc.subject.keywordGalectin-3,NLRP3 inflammasome,TLR4. macrophages,en
dc.relation.page48
dc.identifier.doi10.6342/NTU201602665
dc.rights.note有償授權
dc.date.accepted2016-08-15
dc.contributor.author-college醫學院zh_TW
dc.contributor.author-dept免疫學研究所zh_TW
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