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完整後設資料紀錄
DC 欄位 | 值 | 語言 |
---|---|---|
dc.contributor.advisor | 李心予 | |
dc.contributor.author | Chi-Lun Chang | en |
dc.contributor.author | 章齊倫 | zh_TW |
dc.date.accessioned | 2021-06-13T16:50:13Z | - |
dc.date.available | 2005-07-19 | |
dc.date.copyright | 2005-07-19 | |
dc.date.issued | 2005 | |
dc.date.submitted | 2005-06-23 | |
dc.identifier.citation | Auwerx J (1999): PPARgamma, the ultimate thrifty gene. Diabetologia 42:1033-49.
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dc.identifier.uri | http://tdr.lib.ntu.edu.tw/jspui/handle/123456789/38874 | - |
dc.description.abstract | Lysophosphatidic acid (LPA)是形態與構造十分簡單的小分子水解磷酸脂(lysophopholipid, LPLs),可經由許多不同種類細胞分泌,並且具有一些與蛋白質生長因子十分相似的作用,對細胞的生存、複製、增生及分化都扮演很重要的角色。LPA會經由和細胞表面特異接受器之接合,進而活化各種中下游之細胞基質,達到傳遞訊息的目的。這些接受器分別為LPA1、LPA2及LPA3,均屬於內皮細胞分化基因(Endothelial differentiation gene)的G蛋白接合型的接受器(G protein-coupled receptor)。Interleukin-1β(IL-1β)為一相當重要的促發炎細胞激素(cytokine), 已知與非特異性免疫、血管硬化及腫瘤生成有重要的關係。超氧化物(reactive oxygen species)可由吞噬細胞(phagocytes)所釋放,其功能為殺死細菌並且調控許\\多發炎反應相關的細胞激素。在血管硬化的過程中,巨噬細胞在吞噬大量的氧化低密度脂蛋白後,會進一步形成泡沫細胞,為此疾病的一重要指標。在本研究中,使用RT-PCR,real-time PCR,西方墨點法和流式細胞儀等實驗方法,探討LPA對小鼠巨噬細胞IL-1β的調控機制及對發炎反應相關功能之影響。首先我們發現LPA1及LPA2的mRNA在小鼠J774A.1及RAW264.7細胞株中表現。接著藉由calcium imaging assay,我們觀察到細胞內鈣離子濃度在LPA處理後有顯著的增加,確定了LPA對於此種細胞的活化作用。此外,我們也發現IL-1β在mRNA、蛋白質各個不同層次的表現皆受到LPA誘導而增加,且生成量的多寡,與處理時間以及濃度有關;且Gi, Rho, NF-kappaB, p38 MAPK,和PI3K的訊息傳遞都參與在這個調控過程中。藉由流式細胞儀我們更進一步發現LPA造成巨噬細胞超氧化物生成增加。同時結果也顯示由LPA所誘導的IL-1β及ROS又可更進一步的調控IL-β。最後我們使用DiI螢光標定的OxLDL,發現到LPA會促進巨噬細胞吞噬OxLDL,因而證明了LPA確實在血管硬化上扮演了重要的角色。 | zh_TW |
dc.description.abstract | Lysophophatidic acid (LPA) is a platelet-enriched low molecular weight lysophospholipid (LPL) with multiple biological functions. These biological activities elicited by LPA are mediated through its binding to a series of G protein-coupled receptors: LPA1, LPA2, and LPA3. IL-1β, a major pro-inflammatory cytokine secreted by multiple cell types, plays an important role in innate immunity, inflammation and tumorigenesis. Reactive oxygen species (ROS) are bacteria killing reagents and also act as a mediator in regulation of multiple signaling pathways. The relationship between ROS and inflammatory cytokine is well characterized. OxLDL uptake by macrophages, also known as fatty streak, is an important indicator in atherosclerosis. From our previous studies, we found that LPA induce IL-1β expression in mouse peritoneal macrophages. In this study, we intended to investigate the molecular mechanisms involved in LPA-regulated IL-1β expression and elucidate inflammation-related functions regulated by LPA in J774A.1 cells. By calcium imaging analysis, we found that calcium mobilization was induces immediately after 1microM LPA treatment. RT-PCR analysis showed that both LPA1 and LPA2 receptors were expressed in J774A.1 and RAW246.7 cells, another commonly used mouse macrophage cell line. Using specific pharmacological blockers and real-time PCR analysis, we delineated that LPA-induced IL-1β mRNA expression is mediated through Rho-, Gi-, NF-kappaB-, p38 MAPK-, and PI3K-dependent pathways. Furthermore, reactive oxygen species (ROS) production in J774A.1 and RAW264.7 cells was increased by LPA dosage-dependently. The LPA-induced ROS production could be partially inhibited by C3 and pertussis toxin (PTx). Furthermore, LPA-induced IL-1β and ROS also play a physiological role by regulating IL-1β expression. Last but not least, fluorescence labeled DiI-OxLDL uptake is also upregulated by LPA in J774A.1 cells. In conclusion, our results elucidated the molecular mechanisms by which LPA-induced IL-1β production and also indicated that LPA is involved in the processes of inflammation and inflammation-related disease, atherosclerosis, in mouse macrophages. | en |
dc.description.provenance | Made available in DSpace on 2021-06-13T16:50:13Z (GMT). No. of bitstreams: 1 ntu-94-R92b41005-1.pdf: 958214 bytes, checksum: d08d2cc4acfa5fbd478b44fb43569178 (MD5) Previous issue date: 2005 | en |
dc.description.tableofcontents | 中文摘要 ………………………………………………………………. I
Abstract ……………………………………………………………… II Introduction …………………………………………………………… 1 Lysophosphatidic acid (LPA) ………………..………………………………… 1 Macrophages ………………………………………………………………… 3 Interleukin-1 …………………………………………………………………. 4 Reactive oxygen species (ROS) ……………………………………………... 5 Atherosclerosis ………………………………………………………………. 7 LPA and atherosclerosis ………………………………………………………. 8 Material and Methods Reagents ………….…………………………...……………………………… 11 Cell culture ………….……………………………...………………………… 11 LPA stimulation ……….……………………………...……………………… 12 Calcium imaging assay ……….…………………………...………………….. 12 RNA isolation and RT-PCR ……….………………………...……………….. 12 Real-time PCR analysis ………………….……………………...……………. 13 Western bolt analysis …………………….……………………...…………… 13 Chemical inhibition ……………………….………………………...………... 14 Intracellular reactive oxygen species (ROS) measurement …………………... 14 Cell proliferation assay ………………………………………...…………….. 15 Cell cycle analysis …………………………………………...……………… 15 Low-density lipoprotein (LDL) labeling and modification………...………… 15 DiI-OxLDL uptake assay ……………………………………………...………16 Statistical analysis ……………………………………………………...…….. 16 Results ………………………………………………………………… 17 LPA receptors expression profiles in J774A.1 and RAW264.7 cells ………... 17 LPA-induced calcium mobilization in J774A.1 cells ………………………… 17 LPA-induced interleukin-1β (IL-1β) expression in J774A.1 cells through a dosage-dependent manner ………………………………………………. 17 LPA-induced interleukin-1β (IL-1β) expression in J774A.1 cells through a time-dependent manner ………………………………………………. 18 LPA-induced IL-1β expression is mediated through Rho-, Gi-, NF-kappaB-, p38 MAPK-, PI3K-dependent but MEK1/MAPK- and PLC-independent pathways …………………………………………………………………. 19 IL-1 receptor antagonist (IL-1ra) inhibits LPA-induced IL-1β expression in J774A.1 cells ………………………………………………..……………. 20 LPA-induced cell proliferation and S/G2 phase percentage in J774A.1 cells ... 21 LPA-induced reactive oxygen species (ROS) production in J774A.1 and RAW264.7 cells ………………………………………………………... 21 LPA-induced ROS production is mediated through Rho-, and Gi-dependent pathways ………………………………………………………………….. 22 LPA-induced ROS is involved in IL-1β production …………………………. 22 LPA-induced DiI-OxLDL uptake in J774A.1 cells ………………………… 23 IL-1 receptor antagonist (IL-1ra) had no inhibitory effect on LPA-induced DiI-OxLDL uptake in J774A.1 cells ……………………………………... 23 Discussion …………………………………………………………….. 25 References …………………………………………………………….. 32 Tables …………………………………………………………………. 46 Figures ………………………………………………………………... 49 | |
dc.language.iso | en | |
dc.title | 水解磷酸脂誘導小鼠巨噬細胞介白素-1β表達,過氧化物生成,與氧化低密度脂蛋白攝入之研究 | zh_TW |
dc.title | Lysophosphatidic acid Induces Interleukin-1β Expression, Reactive Oxygen Species Production, and Oxidized LDL Uptake in Mouse Macrophages | en |
dc.type | Thesis | |
dc.date.schoolyear | 93-2 | |
dc.description.degree | 碩士 | |
dc.contributor.oralexamcommittee | 陳俊宏,潘建源,周秀慧,黃偉邦 | |
dc.subject.keyword | 水解磷酸脂,巨噬細胞,IL-1β過氧化物,氧化低密度脂蛋白攝入, | zh_TW |
dc.subject.keyword | LPA,IL-1β,ROS,Ox-LDL uptake, | en |
dc.relation.page | 62 | |
dc.rights.note | 有償授權 | |
dc.date.accepted | 2005-06-24 | |
dc.contributor.author-college | 生命科學院 | zh_TW |
dc.contributor.author-dept | 動物學研究研究所 | zh_TW |
顯示於系所單位: | 動物學研究所 |
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