運用老鼠鼻腔內定植人類表皮葡萄球菌之策略以降低SARS-CoV-2之核殼蛋白於肺中誘導的介白素6;The strategy of using mice nasally colonized human Staphylococcus epidermidis to minimize the levels of lung interleukin-6 induced by SARS-CoV-2 nucleocapsid phosphoprotein

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題名:	運用老鼠鼻腔內定植人類表皮葡萄球菌之策略以降低SARS-CoV-2之核殼蛋白於肺中誘導的介白素6;The strategy of using mice nasally colonized human Staphylococcus epidermidis to minimize the levels of lung interleukin-6 induced by SARS-CoV-2 nucleocapsid phosphoprotein
作者:	楊仁和;Yang, Jen-Ho
貢獻者:	生物醫學工程研究所
關鍵詞:	表皮葡萄球菌;新冠病毒;核殼蛋白;介白素6;Staphylococcus epidermidis;SARS-CoV-2;nucleocapsid phosphoprotein;interleukin-6
日期:	2021-01-26
上傳時間:	2021-03-18 16:51:13 (UTC+8)
出版者:	國立中央大學
摘要:	據報導，嚴重急性呼吸綜合症候群冠狀病毒2 (SARS-CoV-2) 的感染可引發過度的IL-6信號傳導，包括有助於2019年重症冠狀病毒疫情 (COVID-19) 多重器官衰竭的細胞因子風暴。使用人源化的小鼠模型，我們證明鼻腔接種SARS-CoV-2的核帽磷蛋白 (NPP)增加支氣管肺泡灌洗液 (BALF) 中IL-6含量。對表皮葡萄球菌 (S. epidermidis) 定植的小鼠鼻腔施用液態辛酸葵酸椰油酯 (LCC) 可以顯著減輕NPP誘導的IL-6。此外，表皮葡萄球菌介導LCC發酵產生電力和丁酸，分別促進細胞定植和激活游離脂肪酸受體2 (Ffar2)。抑制Ffar2阻礙了表皮葡萄球菌加入LCC對減少NPP誘導IL-6的降低作用。綜上所述，本研究結果表明，鼻腔表皮葡萄球菌可能是緩解SARS-CoV-2呼吸道感染所引起的細胞因子風暴的第一道防線的一部分。本研究是與本實驗室的博士生高銘杉學長共同完成的。本人的貢獻，包括純化蛋白質、病毒接種、小鼠實驗、IL-6檢測、細菌篩選、肺液採集、電壓測量、DNA純化、PCR反應、細菌發酵以及HPLC實驗等，在本論文中均有介紹。作為共同作者，題為「Nasal colonization of Staphylococcus epidermidis mitigates SARS-CoV-2 nucleocapsid phosphoprotein-induced interleukin-6 in the lung」的手稿標題和摘要作為附錄。 ;It has been reported that infection by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) triggered excessive interleukin (IL)-6 signaling, leading to a myriad of biological effects including a cytokine storm that contributed to multiple organ failure in coronavirus disease 2019 (COVID-19). Using a humanized mouse model, we have demonstrated that nasal inoculation of nucleocapsid phosphoprotein (NPP) of SARS-CoV-2 increased IL-6 content in bronchoalveolar lavage fluid (BALF). Nasal administration of liquid coco-caprylate/caprate (LCC) onto Staphylococcus epidermidis (S. epidermidis)-colonized mice significantly diminished NPP-induced IL-6. Furthermore, S. epidermidis- mediated LCC fermentation to generate electricity and butyric acid that promoted bacterial colonization and activated free fatty acid receptor 2 (Ffar2), respectively. Inhibition of Ffar2 suppressed the effect of S. epidermidis plus LCC on the reduction of NPP-induced IL-6. In summary, results in this study suggest that nasal S. epidermidis may be part of the first line of defense in ameliorating a cytokine storm induced by airway infection of SARS-CoV-2. This study has been conducted with Mr. Ming Shan Kao, a PhD student in our laboratory. My contributions including protein purification, virus inoculation, mouse experiments, Interleukin (IL)-6 assays, bacterial screening, lung fluid collection, voltage measurement, DNA purification, PCR reaction, bacterial fermentation and HPLC experiments, have been described in this thesis. As a co-author, the title and abstract of a manuscript entitled” Nasal colonization of Staphylococcus epidermidis mitigates SARS-CoV-2 nucleocapsid phosphoprotein-induced interleukin-6 in the lung” have been attached as an appendix.
顯示於類別:	[生物醫學工程研究所 ] 博碩士論文

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