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  • 學位論文

研究酵母多醣體在數突狀細胞的影響:細胞激素表現廓型,細胞成熟及刺激T細胞分化

Effect of zymosan on dendritic cells:cytokine expression profile, cell matiration and priming of T cell differention

指導教授 : 楊寧蓀

摘要


利用熱水浸泡不同蕈類或樹生真菌類所得到的生物萃取物,在幾個世紀以來,已經被使用於民俗草藥治療,特別是傳統中藥。這種具有保健及特殊醫療特性的治療方式在現今仍然持續被使用。Glucans是自然界的多醣體,由D-glucopyranosyl組成,廣泛存在穀類、植物、海藻、細菌、真菌、蕈類及酵母菌中。Zymosan是酵母菌細胞壁多醣體的衍生物,由β-glucan、mannans、chitins所組成,其中β-glucan佔了組成成份的50%-60%。在本篇研究中,我們進行zymosan刺激人類樹突狀細胞的實驗,以探討不同細胞激素IL-6、TNF-α、GM-CSF、 IL-1α、 IL-1β、 IL-10和MCP-1的表現活力,本研究發現zymosan對這些細胞激素具有專一性且不同程度的影響作用。最重要的是,我們觀察到受zymosan刺激的樹突狀細胞能夠有效地引發GM-CSF的表現,可能進而影響T cell之增生,而這樣的細胞訊息傳遞路徑迥異於經由LPS來刺激樹突狀細胞的效果。在實驗室先前的實驗結果中,利用將從山藥(Dioscorea batatas)塊莖萃取出來的,大部分由glucan組成的植物萃取物,稱為DsCE-I,應用在老鼠皮膚之實驗系統中,也同樣具有活化GM-CSF transgenic promoter之活性。因此我們推論zymosan或是亦具有類似β-glucan結構的生物萃取物,有可能也同樣經由GM-CSF訊息傳遞路徑,而發展成有潛力的腫瘤疫苗佐劑或是增強免疫能力的植物藥劑。另外,藉由現今研究人類樹突狀細胞的技術平台,我們預期將可以系統性地篩選有用之植化物、草藥或生物萃取物,使其能夠成為腫瘤疫苗佐劑或免疫調節試劑的候選藥物或植物性藥物(botanical drugs)。

並列摘要


Hot water extracts from a variety of mushrooms and tree fungi have been used for centuries as folk remedies, especially in traditional Chinese medicine. Today, they are still commonly used in many cultures for general health care and specific therapeutic properties. Glucans are a group of naturally occurring polysaccharides comprised of D-glucopyranosyl units and can be found in a wide variety of cereals, plants, algae, bacteria, fungi, mushrooms and yeasts. Zymosan, a crude extract of yeast cell wall component from Saccaromyces cerevisiae, is composed of β-glucans, mannans, and chitins. In this study, specific and differential effects of zymosan on expression of several key cytokines, including interleukin-6 (IL-6), tumor necrosis factor-α (TNF-α), granulocyte-macrophage colony-stimulating factor (GM-CSF), IL-1α, IL-1β, IL-10 and monocyte chemoattractant protein-1 (MCP-1), were investigated in human dendritic cells (hDCs) in primary cultures. This study showed that zymosan-treated DCs can effectively induce GM-CSF expression, which in turn may stimulate T cell proliferation, and this effect is distinct from the activities observed for hDCs when stimulated with LPS. In our lab previous data, we also have observed that a plant extract fraction (DsCE-I) containing mainly glucan isolated from Dioscorea batatas plant showed a similar effect on the induction of GM-CSF transgenic promoter activity in mouse skin tissue. Therefore, we suggest that zymosan or similar β-glucan components from plant tissues may be developed as useful adjuvants or agents for stimulating adaptive immune activities, with a specific by mediation via the GM-CSF signal transduction system. Our studies also suggest that the current DC based system may be employed for future systematic screening and evaluation of potent and functionally-specific tumor vaccine adjuvants or immune-modulatory agents.

參考文獻


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