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標題: | 激活脂聯素一型接受體惡化發炎性腸道疾病 Activation of adiponectin receptor 1 exacerbates inflammatory bowel disease |
作者: | Yu-Ju Peng 彭裕如 |
指導教授: | 丁詩同(Shih-Torng Ding) |
關鍵字: | 發炎性腸道疾病,脂聯素,脂聯素一型接受體,嗜中性球,介白素8,趨化因子, inflammatory bowel disease,adiponectin,adiponectin receptor 1,neutrophil,IL-8,chemokine, |
出版年 : | 2019 |
學位: | 博士 |
摘要: | 脂肪細胞最為人熟知的功能為透過三酸甘油脂的合成和分解來調控能量平衡,近年來的研究亦發現脂肪細胞具有內分泌功能,產生脂肪激素調節不同的生理功能。脂聯素是種脂肪細胞激素,有調控生物體能量平衡和抗發炎的功用。然而,脂聯素和其接受體在腸道發炎扮演的角色卻是有爭議之處,且對嗜中性免疫細胞的影響仍是未知。故本次研究希望釐清脂聯素一型接受體對腸炎和嗜中性免疫細胞的影響。首先以化學藥劑葡聚糖硫酸引起脂聯素一型接受體轉殖基因小鼠產生急性腸炎,並以脂聯素重組蛋白處理腸道上皮細胞株和巨噬細胞株。實驗結果顯示,脂聯素一型接受體轉殖基因小鼠會罹患較嚴重的急性腸炎,且脂聯素重組蛋白會促進腸道上皮細胞和巨噬細胞表現發炎因子。在無誘導急性腸炎的轉殖基因小鼠腸道有較高量的發炎因子環氧合酶2和嗜中性免疫細胞驅化因子 (neutrophil chemokines, CXCL1,CXCL2和CXCL5)表現,且腸道有較多的嗜中性免疫細胞浸潤。本研究結果顯示脂聯素和其一型接受體可能會藉由兩種方式惡化腸道發炎: 1. 脂聯素和其一型接受體訊號會促進發炎因子的表現。2. 脂聯素一型接受體增加嗜中性免疫細胞驅化因子,造成腸道過量的嗜中性免疫細胞浸潤,過度活化的免疫反應造成嚴重的腸道發炎。 Adiponectin (ADN) is an adipokine mainly derived from adipose tissue. It binds to adiponectin receptor 1 and 2 (AdipoR1 and R2) to exert its function in regulating whole-body energy homeostasis and inflammatory responses. However, the role of ADN-AdipoR1 signaling in intestinal inflammation is controversial, and its role in the regulation of neutrophils is still unclear. Our goal was to clarify the role of AdipoR1 signaling in colitis and the effects on neutrophils. We generated porcine AdipoR1 transgenic mice (pAdipoR1 mice) and induced murine colitis using dextran sulfate sodium (DSS) to study the potential role of AdipoR1 in inflammatory bowel disease. THP-1 macrophage and HT-29 colon epithelial cells were treated with ADN recombinant protein to study the effects of ADN expression on inflammation. After inducing murine colitis, pAdipoR1 mice developed more severe pathogenesis than wild-type (WT) mice. Treatment with ADN increased the expression of pro-inflammatory factors in THP-1 and HT-29 cells in association with the increased expression of cyclooxygenase2 (cox2), neutrophil chemokines (CXCL1, CXCL2 and CXCL5), and the infiltration of neutrophils were increased in the colon of pAdipoR1 mice. Current study showed that AdipoR1 signaling exacerbated colonic inflammation through two possible mechanisms. First, ADN-AdipoR1 signaling increased pro-inflammatory factors. Second, AdipoR1 enhanced neutrophil chemokine expression and neutrophils infiltration into the colonic tissue to increase inflammation. |
URI: | http://tdr.lib.ntu.edu.tw/jspui/handle/123456789/71500 |
DOI: | 10.6342/NTU201900318 |
全文授權: | 有償授權 |
顯示於系所單位: | 動物科學技術學系 |
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