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標題: | 探討台灣紫芝多醣體對免疫抑制性巨噬細胞的影響 Effects of Ganoderma formosanum polysaccharides on immunosuppressive macrophages |
作者: | Hsien-Chan Chiu 邱顯展 |
指導教授: | 陳俊任(Chun-Jen Chen) |
關鍵字: | 台灣紫芝,多醣體,骨髓衍生巨噬細胞,T 細胞增生,腫瘤相關巨噬細胞, Ganoderma formosanum,extracellular polysaccharide,bone marrow derived macrophages (BMDMs),T cell proliferation,tumor associated macrophages (TAMs), |
出版年 : | 2018 |
學位: | 碩士 |
摘要: | 台灣紫芝 (Ganoderma formosanum)為台灣特有靈芝品種,本實驗室以液態醱酵培養台灣紫芝菌絲體,並以膠體過濾純化出台灣紫芝胞外多醣體PS-F2。先前的研究指出將PS-F2以腹腔注射或口服方式給予帶有腫瘤之小鼠,具有抗腫瘤功用;此外先前研究結果顯示PS-F2可以透過TLR-4, CR3, Dectin-1等受器活化下游的訊息傳導,導致巨噬細胞被活化。目前已知巨噬細胞可分化為促發炎反應的M1巨噬細胞及抑制發炎反應的M2巨噬細胞,而在腫瘤微環境中,tumor-associated macrophage (TAM)通常受腫瘤細胞影響而分化為M2-like巨噬細胞,進而抑制抗腫瘤之免疫反應。基於先前之研究成果,本研究想進一步探討PS-F2是否可將TAM轉變成M1型態巨噬細胞,而達到抑制腫瘤的效果。結果顯示PS-F2可刺激M2巨噬細胞分泌發炎細胞激素TNF-α及IL-6,並提升細胞表面CD86及CD40之表現。此外,PS-F2之刺激也可誘發M1巨噬細胞標誌基因iNOS、IL-12、IL-6、IL-1β、IFN-β及TNF-α之表現,並抑制M2巨噬細胞標誌基因arginase 1、TGF-β之表現。從C26腫瘤分離出之TAM以PS-F2刺激後,在基因表現和細胞激素的分泌亦可得到相似之結果。此外我們發現M2巨噬細胞抑制T細胞增生的能力在給予PS-F2後有減緩的情形,這些結果顯示PS-F2之刺激可促使TAM由M2-like轉變成為M1型巨噬細胞,進而達到抑制腫瘤生長之效果。 Ganoderma formosanum is a unique species of Ganoderma isolated in Taiwan. Our previous studies showed that PS-F2, an extracellular polysaccharide fraction purified from the submerged culture of G. formosanum, could active macrophages by Toll-like receptor (TLR)-4, complement receptor (CR) 3 and Dectin-1, and serve as a Th1 adjuvant in vivo. PS-F2 also exhibits antitumor activity when given intraperitoneally or orally to mice. In this study, we investigated whether PS-F2 exerts the antitumor activity via modulating the polarization of M2-like tumor-associated macrophages (TAMs). Our data showed that in both M0 and IL-4-polarized M2 bone marrow derived macrophages (BMDMs), PS-F2 stimulated the production of proinflammatory cytokines TNF-α and IL-6, and the surface expression of CD86, CD40. In addition, PS-F2 stimulated the expression of M1 macrophage signature genes iNOS, IL-12, IL-6, IL-1β, IFN-β and TNF-α, while downregulating the expression of M2 macrophage-related genes arginase1, TGF-β, and Ym-1. Similar results were obtained when primary TAMs isolated from C26 tumor-bearing mice were treated with PS-F2. Furthermore, when M2 macrophages were treated with PS-F2, their suppressive effect on T cell proliferation was alleviated. Taken together, our data demonstrate that PS-F2 stimulation can repolarize protumor M2-like TAMs into antitumor M1 macrophages, resulting in the suppression of tumor growth. |
URI: | http://tdr.lib.ntu.edu.tw/jspui/handle/123456789/70406 |
DOI: | 10.6342/NTU201802984 |
全文授權: | 有償授權 |
顯示於系所單位: | 生化科技學系 |
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