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  • 學位論文

半乳糖凝集素-3在介白素-1β的表現中所扮演的角色

The role of Galectin-3 in IL-1β production.

指導教授 : 賴明宗
共同指導教授 : 劉扶東(Fu-Tong Liu)

摘要


半乳凝集素-3是一種β-半乳糖苷結合凝集素,它對於各種生物功能,例如細胞-細胞相互作用、細胞週期調控、細胞生長、發炎反應和腫瘤發展進程中扮演重要角色。此外,研究也顯示,半乳糖凝集素-3亦可調節各種傳染病和某些特定類型的癌症。然而,半乳凝集素-3在發炎反應中所扮演的角色仍未被釐清。我們使用了骨髓源巨噬細胞來進行研究,探討半乳凝集素-3在脂多醣所誘發的發炎反應中所扮演的角色。結果發現,發炎性細胞激素和發炎小體的前驅物的表現在半乳凝集素-3缺乏的巨噬細胞中有顯著下降的情形。進一步也發現類鐸受體-4下游的信號也較弱。然而,在我們的動物模型所做出來的結果卻認為半乳凝集素-3是一個負向調控者,這個結果暗示著,半乳凝集素-3在不同亞型的巨噬細胞中可能扮演著不同的角色。從我們的實驗結果可以歸納出,內源性半乳凝集素-3在不同類型的巨噬細胞中可能有著不同的功能。未來我們會繼續著重在不同亞型的巨噬細胞,進一步去釐清半乳凝集素-3在發炎小體活化中所扮演的角色,讓我們能更清楚地知道半乳凝集素-3具有怎樣的功能。

並列摘要


Galectin-3 is a beta-galactoside-binding lectin that participates in orchestrating various biological functions such as cell-cell interaction, cell cycle control, cell growth, inflammation and tumor progression. Also, studies have shown that galectin-3 is involved in the regulation of various infectious diseases and certain type of cancer. Nevertheless, a number of issues related to the role of galectin-3 in inflammation remain to be addressed. Here, we investigated the role of galectin-3 in inflammatory responses triggered by LPS treatment within bone marrow-derived macrophages. As a result, we found that proinflammatory cytokines and precursors of inflammasomes were significantly downregulated in galecitn-3-deficient macrophages. Moreover, TLR4 downstream signaling was impaired. However, our in vivo assay showed that galectin-3 might be a negative regulator. These results imply that galectin-3 might have different functions in different subtypes of macrophage. In summary, our results suggest that endogenous galectin-3 might play distinct roles in various macrophage subtypes. Additional studies are required to elucidate how endogenous galecitn-3 regulates inflammasome activation in different subtypes of macrophages, which it may also help us understand its role in innate immune system.

參考文獻


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