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研究生(外文):Jung-Hung Su
論文名稱(外文):Menthol Modulates Dendritic Cells Functions and Attenuates Allergic Contact Hypersensitive
指導教授(外文):CHI-CHEN LIN
外文關鍵詞:MentholDendritic cellTh1 CellLPSContact hypersensitive
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樹突狀細胞(Dendritic cell,簡稱:DCs)被認為先天性免疫與適應性免疫間的重要聯結因子。因此,樹突狀細胞(DCs)可視為發展免疫抑制劑最重要的標的。薄荷醇(Menthol)一種可以從薄荷或者其他薄荷相關的植物精油中提煉出來的天然單萜。目前已有許多文獻證實,薄荷醇具有調節免疫的功效,而樹突狀細胞正是免疫調節中扮演重要的角色,然而兩者間的相關性目前尚未明朗化。本研究中,試著讓小鼠骨髓樹突狀細胞在薄荷醇環境下再用LPS(Lipopolysaccharide, 脂多醣)去刺激後觀察其分化狀況。從我們的實驗證實,薄荷醇除了能夠有效降低促炎激素(TNF-α、IL-6)、趨化因子(IL-8、MCP-1)外還可以當LPS刺激樹突狀細胞(DCs)時可以降低IL-12的表現避免誘導成Th1,而這一切的反應並不會影響與MHC或共同刺激物(CD11c、CD40、CD80、CD86)的表現,主要原因是薄荷醇沒有佔用它們與抗原結合的位置和影響其結合的能力。另外,在2,4-二硝基-1-氟苯 (2,4-Dinitro-1-fluorobenzene)-pulsed樹突狀細胞轉移實驗中,發現薄荷醇在接觸型過敏模組中能夠有效減緩體內Th1的反應。綜合以上我們的研究結果顯示,薄荷醇可以有效的調控樹突狀細胞發炎的特性,主要是因為阻礙樹突狀細胞避免引起Th1免疫反應。這樣的結果讓薄荷醇在免疫學上有了新的功能見解,可適用在治療慢性發炎疾病或是因為Th1媒介的自體免疫性疾病。

Dendritic cells (DCs) link innate immune sensing of the environment to the initiation of adaptive immune responses. Accordingly, DCs are considered as a major target in the development of immunomodulators. Menthol is a naturally monoterpene isolated from the essential oil of peppermint or other mint plants. While substantial evidence indicates that menthol possesses immunomodulatory activity, however, the effect of menthol on dendritic cells (DCs) remains unknown. In this study, we investigated the effect of menthol on lipopolysacchride (LPS) stimulated mouse bone marrow-derived DCs activation. Our experimental results show that menthol could reduce the pro-inflammatory cytokines (TNF-α, IL-6), chemokine (IL-8, MCP-1) and Th1 cytokine IL-12 expression on LPS-activated DC and this reduction, however, it did not affect the expression of of MHC or costimulatory (CD11c、CD40、CD80、CD86) molecules and did not influence the ability to take up antigen. Furthermore, menthol also attenuates the Th1-type immune response in 2,4-Dinitro-1-fluorobenzene pulsed DC-transfer model of contact hypersensitive (CHS) in vivo. Collectively, our findings suggest that menthol can manipulate the inflammatory properties of DCs and furthermore, impedes the function of DCs to prime a Th1-mediated immune response. These results provide new insight into the immunopharmacological role of menthol and applied for treatment of chronic inflammatory disorders or Th1-mediated autoimmune diseases.

摘要 i
Abstract ii
目次 iii
表目錄 vi
圖目錄 vii
縮寫表 ix
第一章 文獻回顧 1
1. 文獻回顧 1
1.1 先天性與適應性免疫反應 1
1.2 樹突狀細胞介紹 2
1.3 Th1/Th2細胞 2
1.4 促炎激素/趨化因子介紹 3
2. 接觸型過敏介紹 3
3. 薄荷醇 4
3.1 薄荷醇介紹 4
3.2 薄荷醇結構 4
3.3 薄荷醇生物功能 4
3.3.1 抗發炎 4
3.3.2 抗菌 5
3.3.3 抗癌 5
4. 研究動機與目的 6
5. 論文架構與實驗設計 7
第二章 利用薄荷醇調控樹突狀細胞的功能及減緩接觸性過敏反應 8
1. 緒論 8
2. 材料與方法 9
2.1 Mice and Preparation of Mouse Bone Marrow derived
DCs 9
2.2 Flow Cytometric Analysis 11
2.3 Cytokine Release Assays 11
2.4 2,4-Dinitro-1-fluorobenzene-Induced contact
Hypersensitivity Assay 13
2.5 Quantitative RT-PCR 13
2.6 Reverse transcription-PCR 15
2.7 Statistical Analysis 16
3. 結果 16
3.1 Menthol decreases the cytokine and chemokine production
by LPS –stimulated mouse bone marrow derived DCs 16
3.2 Menthol does not affect the expression of surface
molecules and endocytosis capacity on LPS –stimulated
DCs 18
3.3 Menthol weaken 2,4-Dinitro-1-fluorobenzene induced
contact hypersensitivity (CHS) responses and Th1 immune
response in vivo 18
4. 討論 19
5. 結論 20
6. 參考文獻 21

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