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| DC 欄位 | 值 | 語言 |
|---|---|---|
| dc.contributor.advisor | 許秉寧(Ping-Ning Hsu) | |
| dc.contributor.author | Ling-En Huang | en |
| dc.contributor.author | 黃鈴恩 | zh_TW |
| dc.date.accessioned | 2021-06-08T04:13:32Z | - |
| dc.date.copyright | 2010-09-09 | |
| dc.date.issued | 2010 | |
| dc.date.submitted | 2010-08-16 | |
| dc.identifier.citation | 1. Feldmann M. Development of anti-TNF therapy for rheumatoid arthritis. Nat Rev Immunol. 2002;2(5):364-71.
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| dc.identifier.uri | http://tdr.lib.ntu.edu.tw/jspui/handle/123456789/22184 | - |
| dc.description.abstract | Rheumatoid arthritis is a chronic systemic autoimmune disease which is characterized by synovitis. And it will gradually develop into poly-articular arthritis with the passage of time. The manifest symptoms of rheumatoid arthritis are joint pain; swelling; stiffness; deformation, moreover, the most prominent symptoms are joint swelling and pain. In late stages of RA, deformity of joint and defective joints expanded due to severely damage. Hence, patient could not be self-management further cause adverse effects in family and society. Rheumatoid arthritis processes involving dys-regulation of multiple components of immune system including the adaptive and the innate immune system. Compared to adaptive immunity, the role of innate immunity in the pathogenesis of rheumatoid arthritis is not well being elucidated yet.
C-type lectin is as an effector molecule in the innate immune system, expressed on immune cells specifically. MDL-1 /CLEC5A is a type II trans-membrane protein belonging to the C type lectin superfamily. According to previous publications, MDL-1 be found participate in osteoclastogenesis when partnered with DAP12 and DAP10 in osteoclasts and bone marrow-derived macrophages in mice. Moreover, In animal model of rheumatoid arthritis shows that MDL-1 as key regulator of synovial injury and bone erosion during Rheumatoid Arthritis joint inflammation. Functional blockade of MDL-1 receptor via Mdl1 deletion or treatment with MDL-1-Ig fusion protein reduces the incidence and severity of autoimmune joint inflammation in mice. Neutrophils presence extraordinary numbers in the synovial fluid of patients with RA when disease flares up. But whether MDL-1 could be detect on neutrophil in RA synovial fluid or whether MDL-1 could modulate neutrophil function are uncertainly. Our data displays neutrophils from synovial fluid in RA patients the MDL-1 expression increased compared with the neutrophil from healthy volunteers peripheral blood. This observation also exist in AS and Gout patient. Therefore, immunehistochemical analyses disclosed MDL-1 positive cells in human RA synovial tissue but not in Osteoarthritis (OA) synovial tissue. Further investigation supporting that MDL-1 expression could be promoted by G-CSF in the present of TNF-α which cytokines are related to RA and neutrophil. Although anti-MDL-1 mAb did not have capacity to stimulate neutrophil to secrete TNF-α and IL-10, TLR4 ligands has been shown to stimulate the raise of RANKL on neutrophil in the present of anti-MDL-1 mAb. Moreover, RANKL could promote osteoclastogenesis. In our results show MDL-1 could enhance Ca2+ influx on neutrophil and enhance generation of neutrophil chemotactic activities. All of evidences indicate MDL-1 have some capacity to modulate the pathogenesis of rheumatoid arthritis. The aim and contribution of this research are to investigate what kind of function mediated by MDL-1 on neutrophil in Rheumatoid arthritis. In the future, expecting that apply MDL-1 related molecule to pharmacological application in RA therapy and further improve patient’s quality of life. | en |
| dc.description.provenance | Made available in DSpace on 2021-06-08T04:13:32Z (GMT). No. of bitstreams: 1 ntu-99-R96b42022-1.pdf: 3609967 bytes, checksum: 3b9a22186148700e431c890059e92393 (MD5) Previous issue date: 2010 | en |
| dc.description.tableofcontents | 口試委員會審定書----------------------------------------------------ii
目錄--------------------------------------------------------------- iii 縮寫表--------------------------------------------------------------v 中文摘要------------------------------------------------------------1 英文摘要------------------------------------------------------------3 第一章 緒論 1.1類風濕關節炎-------------------------------------------------6 1.2嗜中性白血球與類風濕性關節炎---------------------------------8 1.3 MDL-1/CLEC5A------------------------------------------------10 1.4 MDL-1/CLEC5A與類風濕關節炎----------------------------------11 第二章 實驗目的及貢獻----------------------------------------------14 第三章 材料與方法--------------------------------------------------16 第四章結果 4.1 類風溼性關節炎關節液中含有大量的嗜中性白血球----------------29 4.2 MDL-1高量的表現在類風濕性關節炎患者的嗜中性白血球表面-------29 4.3 MDL-1表現在類風溼性關節炎患者的關節滑膜組織-----------------30 4.4 MDL-1在嗜中性白血球表面的表達可經由G-CSF加TNF-α所誘導----30 4.5 TLR 2、TLR 4、TLR 5配體可以刺激嗜中性白血球產生活性氧化物------32 4.6在類風濕性關節炎滑膜液的嗜中性白血球無法經MDL-1與TLR訊號協同 作用使之分泌TNF-α或IL-10----------------------------------33 4.7嗜中性白血球經由TLR4和MDL - 1的刺激有助於其表面表現RANKL----35 4.8 嗜中性白血球經由MDL - 1的訊號可促進細胞內鈣離子流動---------36 4.9 嗜中性白血球經由MDL - 1的訊號而增強其趨化作用--------------37 第五章 討論--------------------------------------------------------39 第六章 結論--------------------------------------------------------48 參考文獻-----------------------------------------------------------51 圖表 --------------------------------------------------------------59 | |
| dc.language.iso | zh-TW | |
| dc.subject | 類鐸受體 | zh_TW |
| dc.subject | 類風濕性關節炎 | zh_TW |
| dc.subject | 嗜中性白血球 | zh_TW |
| dc.subject | C-型凝集素 | zh_TW |
| dc.subject | MDL-1(CLEC5A) | zh_TW |
| dc.subject | C-type lectin | en |
| dc.subject | Toll like receptor | en |
| dc.subject | MDL-1(CLEC5A) | en |
| dc.subject | Rheumatoid arthritis | en |
| dc.subject | Neutrophil | en |
| dc.title | 嗜中性白血球上MDL-1(CLEC5A)在類風性關節炎中的角色 | zh_TW |
| dc.title | The role of MDL-1(CLEC5A) on neutrophil in Rheumatoid Arthritis | en |
| dc.type | Thesis | |
| dc.date.schoolyear | 98-2 | |
| dc.description.degree | 碩士 | |
| dc.contributor.coadvisor | 謝世良(Shie-Liang Hsieh) | |
| dc.contributor.oralexamcommittee | 司徒惠康(Huey-Kang Sytwu) | |
| dc.subject.keyword | 類風濕性關節炎,嗜中性白血球,C-型凝集素,MDL-1(CLEC5A),類鐸受體, | zh_TW |
| dc.subject.keyword | Rheumatoid arthritis,Neutrophil,C-type lectin,MDL-1(CLEC5A),Toll like receptor, | en |
| dc.relation.page | 79 | |
| dc.rights.note | 未授權 | |
| dc.date.accepted | 2010-08-17 | |
| dc.contributor.author-college | 醫學院 | zh_TW |
| dc.contributor.author-dept | 免疫學研究所 | zh_TW |
| 顯示於系所單位： | 免疫學研究所 | |
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