鮑魚菇 (Pleurotus cystidiosus) 是臺灣常見菇類，為側耳科 (Pleurotaceae) 側耳屬 (Pleurotus) 真菌，過去文獻指出，鮑魚菇萃取物具有抗高血壓、抗癌細胞增生與降低血糖等多項生物活性，然而卻少有實驗使用純物質進行研究。因此本研究目的以純化鮑魚菇 14 kDa 之蛋白 (Pcy) 為材料，並研究 Pcy 對小鼠腹腔巨噬細胞 (peritoneal macrophage, pMø) 的免疫調節活性與活化路徑。
經實驗結果發現，將 12.5 μg/mL Pcy 與 pMø 共培養，可以活化 pMø 並增強 pMø 吞噬大腸桿菌之活性，增加表面抗原 CD86 與 MHC class II 表現，提高細胞激素 TNF-α 與 IL-1β 分泌量，同時也提高 TNF-α、IL-1β、IL-12p35、IL-12p40、CD38、EGR2 和 IL-10 等細胞激素之基因表現量。另外，Pcy 可以增加 M1 型 CCL3、CCL4 等趨化素基因之表現，以及 M2 型趨化素 CCL17 和 CCL22 基因表現量也會增加。在訊息傳導途徑方面，分別使用 TLR2 與 TLR4 基因剔除小鼠，發現 Pcy 會活化 TLR2-/- 小鼠腹腔巨噬細胞活化產生 TNF-α 與 IL-1β，然而於 TLR4-/- 小鼠之 TNF-α 與 IL-1β 分泌量皆不明顯，因此推測 Pcy 活化小鼠腹腔巨噬細胞之途徑和 TLR4 相關，然而還需進一步研究驗證。由以上實驗結果可知 Pcy 能活化小鼠腹腔巨噬細胞及其表面標誌，提升宿主免疫反應。

Abalone mushroom (Pleurotus cystidious) is one of the most popular edible mushrooms in Asia. Previous studies have shown that extracts from P. cystidious possessed several biological activities including antihypertension, antiproliferation of tumor cells and hypoglycemic effect. However, little research put emphasis on purified protein from P. cystidious. In this study, a 14 kDa immunomodulatory protein, Pcy, was purified from P. cystidious, and the effects of Pcy on activation, differentiation and TLR-signaling pathways of mouse peritoneal macrophages were investigated. According to the results, Pcy could induce phagocytic activity, increase the secretion of TNF-α and IL-1β, and enhance the expression of surface markers CD86 and MHC class II of mouse peritoneal macrophages. Pcy could upregulate mRNA expression of TNF-α, IL-1β, IL-12p35, IL-12p40, CD38, EGR2, and IL-10 cytokines. Pcy could also increase mRNA expression of both M1 and M2 type chemokine genes. Finally, TLR2 and TLR4 knockout mice were used to investigate the signaling pathway. Pcy could still induce macrophages to secrete TNF-α and IL-1β from TLR2 knockout mice, but the same activation was not obvious in TLR4 knockout mice. We suggest that the activation of Pcy on macrophage might relate to TLR4 signaling pathway, and more researches should be done for further confirmation. In conclusion, Pcy is an immunomodulatory protein, which could activated macrophages and strengthen the host immunity.

口試委員會審定書 Ⅰ
致謝 Ⅱ
摘要 Ⅳ
Abstract Ⅴ
目錄 Ⅵ
圖目錄 Ⅸ
第一章 前言 1
第一節 食藥用菇類之生理活性 1
1.1. 食藥用菇類的重要性 1
1.2. 食藥用菇類的抗腫瘤與免疫調節活性 1
1.3. 菇類中已知的生理活性成分 2
1.4. 具生理機能性的菇類蛋白 3
第二節 鮑魚菇簡介 4
2.1. 鮑魚菇分類與特性 4
2.2. 鮑魚菇之營養成分 5
2.3. 鮑魚菇已知成分與功能 5
第三節 免疫調節反應 8
3.1. 先天性免疫反應 9
3.1.1. 單核細胞 (Monocyte) 的生理功能 9
3.1.2. Toll-like receptors 與訊息傳導 10
3.1.3. TLR2 10
3.1.4. TLR4 11
3.1.5. TLR5 12
3.2. 巨噬細胞之免疫反應 12
3.3. 適應性免疫反應 13
3.4. 調節適應性免疫反應 13
3.4.1. 細胞激素 (cytokines) 14
3.4.2. 趨化素 (chemokines) 15
第四節 研究動機與目的 16
第二章 材料與方法 17
第一節 鮑魚菇免疫調節蛋白之純化與鑑定 17
1.1. 鮑魚菇之純化 17
1.2. SDS-PAGE 膠體電泳分析 19
1.3. 醣蛋白染色分析 20
1.4. 血球凝集活性 21
第二節 Pcy 活化小鼠腹腔巨噬細胞之免疫活性 21
第三節 小鼠腹腔巨噬細胞吞噬活性測試 25
第四節 小鼠腹腔巨噬細胞之抗原呈獻能力測試 27
第五節 Pcy 刺激之腹腔巨噬細胞基因表現量之測定 29
第六節 TLRs 與 Pcy 活化巨噬細胞之相關性 32
第七節 統計分析 34
第三章 結果 35
第一節 鮑魚菇蛋白Pcy之純化與性質 35
第二節 Pcy 對小鼠脾細胞之影響 36
第三節 Pcy 對小鼠腹腔巨噬細胞吞噬能力之影響 36
第四節 Pcy 對小鼠腹腔巨噬細胞抗原呈獻能力之影響 37
第五節 Pcy 增加小鼠腹腔巨噬細胞細胞激素之分泌 38
第六節 Pcy 對小鼠腹腔巨噬細胞之細胞激素基因表現量之影響 39
第七節 Pcy對小鼠腹腔巨噬細胞趨化素基因表現量之影響 40
第八節 Pcy活化小鼠巨噬細胞之相關路徑 41
第四章 討論 42
第一節 鮑魚菇蛋白 Pcy 之選擇與純化 42
第二節 Pcy 對小鼠脾臟細胞和巨噬細胞之影響 42
第三節 Pcy 可增加巨噬細胞吞噬能力及抗原呈獻能力 43
第四節 Pcy 可促進細胞激素基因之表現與分泌 44
第五節 Pcy 可增加巨噬細胞趨化素基因之表現 45
第六節 TLRS 路徑與 Pcy 活化巨噬細胞之相關性 46
第五章 結論 47
第六章 參考文獻 48
附錄 60

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