Recycling Agriculture: Recycling of Agricultural WasteDepartment of Food Science Biotechnology / Chiang, En-Pei Isabel / Distinguished Professor
循環農業:農業廢棄物再資源化【食品暨應用生物科技學系/蔣恩沛特聘教授】
論文篇名 英文:N-3 polyunsaturated fatty acids block the trimethylamine-N-oxide- ACE2- TMPRSS2 cascade to inhibit the infection of human endothelial progenitor cells by SARS-CoV-2
中文:N-3 多元不飽和脂肪酸阻斷三甲胺-N-氧化物-ACE2-TMPRSS2級聯反應以抑制 SARS-CoV-2 對人體內皮前驅細胞的感染
期刊名稱 JOURNAL OF NUTRITIONAL BIOCHEMISTRY
發表年份,卷數,起迄頁數 2022, 109, 109102
作者 Chiang, En-Pei Isabel(蔣恩沛); Syu, Jia-Ning; Hung, Hung-Chang; Rodriguez, Raymond L.; Wang, Wei-Jan; Chiang, En -Rung; Chiu, Shao-Chih; Chao, Che-Yi; Tang, Feng-Yao
DOI 10.1016/j.jnutbio.2022.109102
中文摘要 嚴重急性呼吸症候群冠狀病毒2 (SARS-CoV-2) 是一種新型冠狀病毒,可感染多種細胞、並引起細胞激素風暴、過度發炎、急性呼吸窘迫,從而導致呼吸系統和其他關鍵器官衰竭。本研究發現,由腸道微生物群產生的代謝物三甲胺-N-氧化物 (TMAO)會促進 inerleukin-6 (IL-6) 細胞激素產生及人體內皮前驅細胞 (hEPC) 感染 SARS-CoV-2。我們還發現給予二十二碳六烯酸 (DHA) 和二十碳五烯酸 (EPA) N-3 多不飽和脂肪酸的處理會有效阻止 SARS-CoV-2 進入 hEPCN-3 多不飽和脂肪酸的抗感染作用 TMAO 刺激後 hEPCs NF-κB 信號通路的失活、 ACE2 受體表現減少、以及下游跨膜絲氨酸蛋白酶 2 的表達降低有關。DHA EPA 的處理可能透過MAPK/p38/JNK 信號級聯反應的失活和 hEPC microRNA (miR)-221 的負調控, 進一步有效地抑制了 TMAO 介導的 IL-6 蛋白表現。總之,DHA EPA N-3 PUFA 可以有效地預防因TMAO 的刺激下 阻斷 hEPC SARS-CoV-2 IL-6 細胞因子的感染。
英文摘要 Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is a novel coronavirus that infects many types of cells and causes cytokine storms, excessive inflammation, acute respiratory distress to induce failure of respiratory system and other critical organs. In this study, our results showed that trimethylamine-N-oxide (TMAO), a metabolite generated by gut microbiota, acts as a regulatory mediator to enhance the inerleukin-6 (IL-6) cytokine production and the infection of human endothelial progenitor cells (hEPCs) by SARS-CoV-2. Treatment of N-3 polyunsaturated fatty acids (PUFAs) such as docosahexaenoic acid (DHA) and eicosapentaenoic acid (EPA) could effectively block the entry of SARS-CoV-2 in hEPCs. The anti-infection effects of N-3 PUFAs were associated with the inactivation of NF-κB signaling pathway, a decreased expression of the entry receptor angiotensin-converting enzyme 2 (ACE2) and downstream transmembrane serine protease 2 in hEPCs upon the stimulation of TMAO. Treatment of DHA and EPA further effectively inhibited TMAO-mediated expression of IL-6 protein, probably through an inactivation of MAPK/p38/JNK signaling cascades and a downregulation of microRNA (miR)-221 in hEPCs. In conclusion, N-3 PUFAs such as DHA and EPA could effectively act as preventive agents to block the infection of SARS-CoV-2 and IL-6 cytokine production in hEPCs upon the stimulation of TMAO.