Please use this identifier to cite or link to this item: http://hdl.handle.net/11455/36286
標題: 結合不同體學之策略以研究植化物或植物萃取物對 於樹突狀細胞之免疫功能及細胞轉分化之刺激作用
Use of Combinational Omics Approach for Studying Stimulatory Effects of Phyto-chemicals/-extracts on Dendritic cell immunity and Cell Transdifferentiation
作者: 尹書翊
Yin, Shu-Yi
關鍵字: Omics
體學
Phyto-chemicals/-extracts
Dendritic cell
Cell Transdifferentiation
植化物
植物翠取物
樹突狀細胞
細胞轉分化
出版社: 生物科技學研究所
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摘要: 結合體學之新式研究策略已被應用於中西草藥之研究中,尤其是因為傳統草藥涵蓋了多種成分,且具有調控不同分子/細胞作用,而對身體往往造成復合式影響(如免疫調控)。為了能夠有效地探討特定草藥萃取物或植化物對特定生理生化之影響,不同之體學研究方法,如基因體學、蛋白質體學及相關生物資訊工具因而被系統性地整合及應用於本研究中。 在我們最近的研究當中,一種從紫錐菊(一種廣泛被使用於西方之藥用植物)分離出之特定萃取物[BF/S+L/Ep],被探討其對老鼠骨髓來源之樹突狀細胞之免疫調控之作用。我們透過系統性生物資訊分析基因體表現,蛋白質體分析及特定生理活性或表現型分析,試圖了解其對細胞或分子之作用機制。我的實驗結果顯示,[BF/S+L/Ep]能有效率地增進樹突狀細胞於活體內之移動能力及相關細胞生理活性。此外,本研究所預測之細胞內訊號及分子傳遞系統,可能也為紫錐菊或其他具免疫調控活性之藥用植物提供在未來臨床或食品營養應用上之潛在標的。 本研究的另一部份,是針對老鼠骨髓來源之樹突狀細胞(BMDCs)之細胞分化技術進行改善。因為此種細胞已被視為發展細胞療法中之重要實驗模型。我發現IL-4這種用來催化BMDC於體外分化產生之細胞激素,能透過後期培養時段之刺激增強BMDC於活體內之移動能力。相較於傳統方法利用IL-4於培養全程進行刺激,利用這種對IL-4刺激之時段加以調控之方式進行細胞培養,同時也可以用較少量的細胞激素產生出更高產量及純度之BMDC;在細胞活性或品質上,以此法產生BMDC之細胞激素釋出活性及活化CD4+ T細胞增生能力亦能被顯著提升。 本研究的最後一部份,是針對紫草素(Shikonin)對老鼠皮膚之生物性刺激進行研究。透過對基因體及microRNA整體表現之綜合分析,我們的研究結果顯示紫草素對皮膚表面刺激後會明顯促進「表皮-間質細胞轉化」(epithelial–mesenchymal transition)之活性,同時也抑制了與該活性相關microRNAs之表現。我們相信這些研究所提供的結果及發現,提供了先前紫草素之促進傷口癒合及其他免疫調控活性有力的理論證據。
Various omics approaches have been employed and are still considered as highly desirable and useful tools for herbal medicine research, presumably because conventional phytomedicines often utilized multi-factoral formulations, and such phytochemical mixtures are blieved to interact with multiple molecular targets, resulting in composite (e.g., immunomodulatory) effects. In order to globally and integratively evaluate the effects of specific herbal extracts or phytomedicines, in this study various omics approaches including genomics, proteomics, and the associated bio-informatics tools were systematically combined to develop my research systems. For the current study, a specific fraction extracted from a popular western medicinal plant, Echinacea purpurea, namely [BF/S+L/Ep], was investigated for its immunomodulatory effects on mouse bone marrow-derived dendritic cells (BMDCs). Various cellular and molecular effects were revealed using a network knowledge-based approach, and analyzed at the level of genome-wide transcriptome, specific proteome and functional phenotype activities. My experimental results suggest that [BF/S+L/Ep] can efficiently enhance DC mobility and the related cellular physiology in vivo. Moreover, the signaling networks and molecules highlighted in this study provided potentially useful targets for nutritional or clinical application of Echinacea or other medicinal plants for immune-modulation activities. The next part of my study was aimed at improving the in vitro differentiation technology for mouse BMDCs, an important pre-clinical model for future development of DC-based therapeutics. I demonstrate here that IL-4, a key driving factor for the in vitro differentiation of BMDCs, can specifically enhance the in vivo trafficking activity of BMDCs during a late stage in cultivation. With such temporal control of IL-4 stimulation, much less cytokine quantity is needed to generate a high yield of BMDCs with increased purity, increased secretion level of cytokines and a higher capacity to induce proliferation of allogeneic CD4+ T cells, as compared to the conventional method which utilizes a continuous supplement of IL-4 throughout the in vitro cultivation period. For the final part of my study, I investigate the in vivo biological effects of shikonin on mouse skin tissues, now appreciated as a highly important organ for metabolic regulations of the whole body system. Through a cross-examination between the transcriptome and microRNA data sets, I show that topical treatment of shikonin in skin with shikonin can drastically enhance epithelial-mesenchymal transition (EMT) activity and suppress the associated-microRNAs expression in vivo in test skin tissues. I consider these results and findings have provided us with good evidence in supporting of various previous observations on the wound-healing and immune-modulatory activities conferred by shikonins, in vivo and in vitro.
URI: http://hdl.handle.net/11455/36286
其他識別: U0005-1701201212053600
文章連結: http://www.airitilibrary.com/Publication/alDetailedMesh1?DocID=U0005-1701201212053600
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