Ileum Gene Expression in Response to Acute Systemic Inflammation in Mice Chronically Fed Ethanol: Beneficial Effects of Elevated Tissue n-3 PUFAs.
Ileum Gene Expression in Response to Acute Systemic Inflammation in Mice Chronically Fed Ethanol: Beneficial Effects of Elevated Tissue n-3 PUFAs.
复制标题
长期摄入乙醇小鼠回肠基因表达对急性全身炎症的反应：组织n-3 PUFAs升高的有益作用。
DOI：
10.3390/ijms22041582
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发表时间：
2021-02-04
影响因子：
5.6
通讯作者：
Kirpich IA
中科院分区：
文献类型：
--
作者：
Hardesty JE;Warner JB;Song YL;Rouchka EC;McClain CJ;Warner DR;Kirpich IA
长期饮酒会导致肠道功能紊乱，炎症会加剧肠道功能紊乱，并受到不同因素的调节，例如，多不饱和脂肪酸（PUFA）。这些改变的机制还不清楚。在本研究中，对来自WT和fat-1转基因小鼠（其具有升高的内源性n-3 PUFA）的回肠组织进行RNA-seq分析。小鼠长期喂食乙醇（EtOH），并用单次脂多糖（LPS）剂量激发以诱导急性全身炎症。WT和fat-1小鼠在EtOH + LPS处理后均表现出显着的回肠转录组变化。与WT相比，fat-1小鼠上调了与细胞周期和异生物质代谢相关的基因的表达，而促炎细胞因子和促纤维化基因的表达降低。响应于EtOH + LPS，fat-1小鼠具有与抗菌B细胞（APRIL和伊加）相关的基因的表达增加，以及在WT小鼠中未观察到的促恢复巨噬细胞和γδ T细胞的标志物的升高。我们的研究显着扩展了由于EtOH消耗和炎症引起的肠道改变的调控机制的知识，并确定了n-3 PUFA的有益转录作用，这可能是一种可行的营养干预，用于过度饮酒引起的肠道损伤。
Chronic alcohol consumption leads to disturbances in intestinal function which can be exacerbated by inflammation and modulated by different factors, e.g., polyunsaturated fatty acids (PUFAs). The mechanisms underlying these alterations are not well understood. In this study, RNA-seq analysis was performed on ileum tissue from WT and fat-1 transgenic mice (which have elevated endogenous n-3 PUFAs). Mice were chronically fed ethanol (EtOH) and challenged with a single lipopolysaccharide (LPS) dose to induce acute systemic inflammation. Both WT and fat-1 mice exhibited significant ileum transcriptome changes following EtOH + LPS treatment. Compared to WT, fat-1 mice had upregulated expression of genes associated with cell cycle and xenobiotic metabolism, while the expression of pro-inflammatory cytokines and pro-fibrotic genes was decreased. In response to EtOH + LPS, fat-1 mice had an increased expression of genes related to antibacterial B cells (APRIL and IgA), as well as an elevation in markers of pro-restorative macrophages and γδ T cells that was not observed in WT mice. Our study significantly expands the knowledge of regulatory mechanisms underlying intestinal alterations due to EtOH consumption and inflammation and identifies the beneficial transcriptional effects of n-3 PUFAs, which may serve as a viable nutritional intervention for intestinal damage resulting from excessive alcohol consumption.
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影响因子：
2.3
作者：
Kirpich, Irina A.;Feng, Wenke;Wang, Yuhua;Liu, Yanlong;Beier, Juliane I.;Arteel, Gavin E.;Falkner, K. Cameron;Barve, Shirish S.;McClain, Craig J.
通讯作者：
McClain, Craig J.
影响因子：
64.5
作者：
Barros, Rafael Di Marco;Roberts, Natalie A.;Dart, Robin J.;Vantourout, Pierre;Jandke, Anett;Nussbaumer, Oliver;Deban, Livija;Cipolat, Sara;Hart, Rosie;Iannitto, Maria Luisa;Laing, Adam;Spencer-Dene, Bradley;East, Philip;Gibbons, Deena;Irving, Peter M.;Pereira, Pablo;Steinhoff, Ulrich;Hayday, Adrian
通讯作者：
Hayday, Adrian
影响因子：
7.7
作者：
Bidu, Celia;Escoula, Quentin;Bellenger, Jerome
通讯作者：
Bellenger, Jerome
影响因子：
32.4
作者：
He, Bing;Xu, Weifeng;Cerutti, Andrea
通讯作者：
Cerutti, Andrea
影响因子：
12.3
作者：
Kim D;Pertea G;Trapnell C;Pimentel H;Kelley R;Salzberg SL
通讯作者：
Salzberg SL