Active or Autoclaved Akkermansia muciniphila Relieves TNF-α-Induced Inflammation in Intestinal Epithelial Cells Through Distinct Pathways.
Active or Autoclaved Akkermansia muciniphila Relieves TNF-α-Induced Inflammation in Intestinal Epithelial Cells Through Distinct Pathways.
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DOI：
10.3389/fimmu.2021.788638
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发表时间：
2021
影响因子：
7.3
通讯作者：
Tang J
中科院分区：
文献类型：
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作者：
Luo Y;Lan C;Xie K;Li H;Devillard E;He J;Liu L;Cai J;Tian G;Wu A;Ren Z;Chen D;Yu B;Huang Z;Zheng P;Mao X;Yu J;Luo J;Yan H;Wang Q;Wang H;Tang J
肠道炎症是仔猪等幼龄动物健康和生长的主要威胁。作为下一代益生菌，有限的研究表明嗜粘蛋白阿克曼菌可以减轻肠上皮细胞（IEC）的炎症。本研究建立了TNF-α诱导的猪小肠IPEC-J2细胞炎症模型，以评价活性或非活性A.对IEC炎症的影响。当用活性（108拷贝/mL）或非活性（109拷贝/mL）A处理时，IPEC-J2细胞的存活率最高。7.5h时，P < 0.01。用20 ng/mL TNF-α处理，然后用A.与对照组相比，嗜粘蛋白组促炎细胞因子IL-8、IL-1β、IL-6和TNF-α的mRNA水平显著降低（P < 0.05），紧密连接蛋白ZO-1和Occludin的mRNA水平沿着升高（P <0.05）。流式细胞仪分析表明，活性或失活的A。muciniphila可明显抑制炎症IPEC-J2细胞的早期凋亡率和总凋亡率（P < 0.05）。根据转录组测序结果，活性和非活性A. muciniphila可能通过下调钙信号通路中关键基因的表达，或上调细胞周期信号通路中关键基因的表达来抑制细胞凋亡。该菌可能通过下调PI 3 K上游受体基因的表达而减轻IEC的炎症反应。结果表明，A.因此，Muciniphila可能是一种很有前途的靶向肠道炎症的NGP。
Intestinal inflammation is a major threat to the health and growth of young animals such as piglets. As a next-generation probiotics, limited studies have shown that Akkermansia muciniphila could alleviate inflammation of intestinal epithelial cells (IECs). In this study, a TNF-α-induced inflammatory model of IPEC-J2 cells, the intestinal porcine enterocytes, was built to evaluate the effects of active or inactive A. muciniphila on the inflammation of IECs. The viability of IPEC-J2 cells was the highest when treated with active (108 copies/mL) or inactive (109 copies/mL) A. muciniphila for 7.5 h (P < 0.01). Treated with 20 ng/mL of TNF-α and followed by a treatment of A. muciniphila, the mRNA level of proinflammatory cytokines (IL-8, IL-1β, IL-6 and TNF-α) was remarkably reduced (P < 0.05) along with the increased mRNA level of tight junction proteins (ZO-1 and Occludin, P < 0.05). Flow cytometry analysis showed that active or inactive A. muciniphila significantly suppressed the rate of the early and total apoptotic of the inflammatory IPEC-J2 cells (P < 0.05). According to results of transcriptome sequencing, active and inactive A. muciniphila may decline cell apoptosis by down-regulating the expression of key genes in calcium signaling pathway, or up-regulating the expression of key genes in cell cycle signaling pathway. And the bacterium may alleviate the inflammation of IECs by down-regulating the expression of PI3K upstream receptor genes. Our results indicate that A. muciniphila may be a promising NGP targeting intestinal inflammation.