Transcriptomic Analyses Reveal the Protective Immune Regulation of Conjugated Linoleic Acids in Sheep Ruminal Epithelial Cells.

Transcriptomic Analyses Reveal the Protective Immune Regulation of Conjugated Linoleic Acids in Sheep Ruminal Epithelial Cells.
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转录组分析揭示了绵羊瘤胃上皮细胞中共轭亚油酸的保护性免疫调节

DOI:
10.3389/fphys.2020.588082
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发表时间:
2020
影响因子:
4
通讯作者:
Fu Z
Fu Z
中科院分区:
医学2区
文献类型:
--
作者:
Yang C;Lan W;Ye S;Zhu B;Fu Z

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瘤胃上皮不断受到瘤胃内死亡微生物细胞裂解释放的抗原的挑战。然而,瘤胃上皮的先天免疫系统几乎总是能够积极响应这些挑战。瘤胃微生物群与瘤胃上皮内先天免疫细胞之间的相互作用在维持瘤胃免疫耐受和炎症反应的平衡中起着重要作用。我们假设共轭亚油酸(CLA)是瘤胃中一种功能性微生物代谢物,可能有助于瘤胃上皮细胞(RECs)的免疫调节;因此,我们首先建立了一个不朽的REC系,然后研究了CLA对这些REC免疫应答的调节作用。结果表明,通过sv40t诱导永生化,成功建立了REC的长期培养。转录组分析显示,由50:50顺式-9、反式-11:反式-10、顺式-12组成的100 μM CLA混合物显著下调炎症反应相关基因TNF-α、IL-6、CX3CL1、IRF1、ICAM1和EDN1的表达,上调细胞增殖相关基因FGF7、FGF21、EREG、AREG和HBEGF以及脂质代谢相关基因PLIN2、CPT1A、ANGPTL4、ABHD5和SREBF1在LPS刺激下的表达。相应的,GO术语细胞粘附、刺激反应和细胞因子产生的调控和KEGG通路TNF和HIF-1信号,ecm受体相互作用和细胞粘附分子被鉴定为显著下调的基因,而GO术语上皮细胞增殖和上皮细胞迁移调控和KEGG通路PPAR,在LPS刺激下,经cla预处理基因显著上调的RECs中发现了ErbB和脂肪细胞因子信号。这些发现表明,CLA通过抑制促炎过程、促进细胞增殖和调节与免疫应答相关的脂质代谢,赋予rec保护性免疫。
The ruminal epithelium is continuously challenged by antigens released by the lysis of dead microbial cells within the rumen. However, the innate immune system of the ruminal epithelium can almost always actively respond to these challenges. The cross talk between the ruminal microbiota and innate immune cells in the ruminal epithelium has been suggested to play an important role in sustaining the balance of immune tolerance and inflammatory response in the rumen. We hypothesized that conjugated linoleic acid (CLA), a functional microbial metabolite in the rumen, may contribute to the immune regulation in rumen epithelial cells (RECs); therefore, we first established an immortal REC line and then investigated the regulatory effects of CLA on the immune responses in these RECs. The results showed that long-term REC cultures were successfully established via SV40T-induced immortalization. Transcriptome analysis showed that a 100 μM CLA mixture consisting of 50:50 cis-9, trans-11:trans-10, cis-12 CLA significantly downregulated the expression of the inflammatory response-related genes TNF-α, IL-6, CX3CL1, IRF1, ICAM1 and EDN1, and upregulated the expression of the cell proliferation-related genes FGF7, FGF21, EREG, AREG and HBEGF and the lipid metabolism-related genes PLIN2, CPT1A, ANGPTL4, ABHD5 and SREBF1 in the RECs upon LPS stimulation. Correspondingly, the GO terms regulation of cell adhesion, response to stimulus and cytokine production and KEGG pathways TNF and HIF-1 signaling, ECM-receptor interaction and cell adhesion molecules were identified for the significantly downregulated genes, while the GO terms epithelial cell proliferation and regulation of epithelial cell migration and the KEGG pathways PPAR, ErbB and adipocytokine signaling were identified for the RECs with significantly upregulated CLA-pretreated genes upon LPS stimulation. These findings revealed that CLA conferred protective immunity onto the RECs by inhibiting proinflammatory processes, promoting cell proliferation and regulating lipid metabolism related to the immune response.
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