Abstract: | 表面醣蛋白為新型冠狀病毒最豐富之蛋白,但該蛋白對於引發新冠肺炎角色還未完全 明確,對比於綠螢光蛋白,在實驗小鼠鼻腔中點該表面醣蛋白可以在肺部沖洗液中引 發介白素六(IL-6) 、一種被當作免疫風暴指標之蛋白的表現,但在磷酸二酯?(PDE4B) 基因缺陷小鼠中卻無法引發 IL-6 之表現,可見 PDE4B 在 IL-6 訊號傳遞中扮演著重要的 角色,鼠李糖乳桿菌 EH8 亞種 (L. rhamnosus) 之菌絲體發酵產物-丁酸,可以降低PDE4B 之表現量以及 IL-6 在巨噬細胞中的分泌,餵食實驗小鼠菌絲體可以增加共生菌 L. rhamnosus 的數量,小鼠在供給 L. rhamnosus 和菌絲體兩個禮拜後可以降低表面醣 蛋白引發之 PDE4B 表現和 IL-6 分泌,在實驗小鼠餵食游離脂肪酸受體 2(Ffar2) 之抑制 劑 GLPG-0974 後,益生菌效果都會被停止,Ffar2 在腸道-肺部連結可以負調節PDE4B-IL-6 之訊號傳遞將可以做為發展益生菌治療新冠肺炎引發免疫風暴中的一個目標。我與 Pham Minh Tan 一起進行了我的碩士研究工作,他是博士。 我們實驗室的學生。 這項研究 工作提交給營養生物化學雜誌正在審查中。 作為本文的合著者,我的主要貢獻包括在 人物圖例中的描述。;The most abundant protein of SARS-CoV-2 is membrane glycoprotein, but the role of this protein in COVID-19 is unclear. The intranasal administration of membrane glycoprotein significantly increased IL-6 in BALF in mice compared to green fluorescent protein (GFP)-inoculated mice. Asignificant decrease was observed in IL-6 levels effected by membrane glycoprotein in PDE4B knockout mice, showing that PDE4B is essential to the process of IL-6 signaling. In macrophages, butyric acid is produced by L.rhamnosus EH8 strain fermentation, which inhibits the PDE4B and affects the release of IL-6. Mice fed mycelia had higher relative abundances of commensal L. rhamnosus. Feeding L. rhamnosus with mycelia for two weeks significantly reduced PDE4Band IL-6 in mice. In mice treated with GLPG-0974, the probiotic effect of L. rhamnosus with mycelia was decreased. In COVID-19, Ffar2 may activate the gut-lung axis for down-regulating the PDE4B-IL-6 signaling. Treatment of cytokine storms with probiotics may be applicable to this target. I conducted my master researcher work withPham Minh Tan who is a PhD student in our lab. This research work submitted to the Journal of Nutritional Biochemistry under review. As a co-author for this paper, my major contributions including described in figure legends. |