Short-Chain Fatty Acids Regulate the Immune Responses via G Protein-Coupled Receptor 41 in Bovine Rumen Epithelial Cells
Short-Chain Fatty Acids Regulate the Immune Responses via G Protein-Coupled Receptor 41 in Bovine Rumen Epithelial Cells
复制标题
短链脂肪酸通过 G 蛋白偶联受体 41 调节牛瘤胃上皮细胞的免疫反应
DOI：
10.3389/fimmu.2019.02042
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发表时间：
2019-08
影响因子：
7.3
通讯作者：
Zhao Guoqi
中科院分区：
文献类型：
--
作者：
Zhan Kang;Gong Xiaoxiao;Chen Yinyin;Jiang Maocheng;Yang Tianyu;Zhao Guoqi
当来自瘤胃中死亡微生物群细胞的裂解的抗原受到攻击时，瘤胃免疫系统经常受到影响。而瘤胃上皮天然免疫系统对感染有积极的反应。先前的研究表明，G蛋白偶联受体41（GPR 41）是短链脂肪酸（SCFAs）的受体。我们推测，瘤胃中最丰富的微生物代谢产物SCFAs可能通过GPR 41调节牛瘤胃上皮细胞（BRECs）的免疫反应。因此，本研究的目的是首先建立一个永生化的BRECs细胞系，并研究SCFAs和GPR 41对BRECs天然免疫应答的调节作用。这些结果表明，长期培养的BRECs建立SV 40 T诱导的永生化。通过转录组分析，20 mM SCFA浓度显著增强了GPR 41、IL 1 β、TNFα、趋化因子和免疫屏障基因的水平。与转录组结果一致，通过qRT-PCR，与对照BREC相比，用20 mM SCFA处理的BREC中GPR 41、IL 1 β、TNFα和趋化因子的表达显著上调。值得注意的是，与用20 mM SCFA处理的野生型BREC相比，用20 mM SCFA处理的GPR 41敲低（GPR 41 KD）BREC显著增强促炎细胞因子IL 1 β和TNFα表达，但降低了CCL 20、CXCL 2、CXCL 3、CXCL 5、CXCL 8、CXCL 14、Occludin和ZO-1的表达。此外，GPR 41 mRNA表达与CCL 20、CXCL 2、CXCL 3、CXCL 8、CXCL 14和ZO-1正相关。这些发现表明，SCFAs调节GPR 41介导的参与免疫细胞募集和上皮免疫屏障的基因水平，从而介导BRECs中的保护性先天免疫。
The rumen immune system often suffers when challenging antigens from lysis of dead microbiota cells in the rumen. However, the rumen epithelium innate immune system can actively respond to the infection. Previous studies have demonstrated G protein-coupled receptors 41 (GPR41) as receptors for short chain fatty acids (SCFAs) in human. We hypothesized that SCFAs, the most abundant microbial metabolites in rumen, may regulate the immune responses by GPR41 in bovine rumen epithelial cells (BRECs). Therefore, the objective of study was to firstly establish an immortal BRECs line and investigate the regulatory effects of SCFAs and GPR41 on innate immunity responses in BRECs. These results showed that long-term BRECs cultures were established by SV40T-induced immortalization. The concentrations of 20 mM SCFAs significantly enhanced the levels of GPR41, IL1β, TNFα, chemokines, and immune barrier genes by transcriptome analysis. Consistent with transcriptome results, the expression of GPR41, IL1β, TNFα, and chemokines were markedly upregulated in BRECs treated with 20 mM SCFAs by qRT-PCR compared with control BRECs. Remarkably, the GPR41 knockdown (GPR41KD) BRECs treated with 20 mM SCFAs significantly enhanced the proinflammatory cytokines IL1β and TNFα expression compared with wild type BRECs treated with 20 mM SCFAs, but reduced the expression of CCL20, CXCL2, CXCL3, CXCL5, CXCL8, CXCL14, Occludin, and ZO-1. Moreover, GPR41 mRNA expression is positively correlated with CCL20, CXCL2, CXCL3, CXCL8, CXCL14, and ZO-1. These findings revealed that SCFAs regulate GPR41-mediated levels of genes involved in immune cell recruitment and epithelial immune barrier and thereby mediate protective innate immunity in BRECs.
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DOI：
10.1007/s11626-016-0082-5
发表时间：
2016
期刊：
In Vitro Cellular & Developmental Biology - Animal
影响因子：
--
作者：
K. Zhan;Miao Lin;Ming-mei Liu;Yang-Nan Sui;Guoqi Zhao
通讯作者：
K. Zhan;Miao Lin;Ming-mei Liu;Yang-Nan Sui;Guoqi Zhao
DOI：
10.1016/s0006-291x(03)00488-1
发表时间：
2003-04-18
影响因子：
3.1
作者：
Nilsson, NE;Kotarsky, K;Olde, B
通讯作者：
Olde, B
DOI：
--
发表时间：
2009
期刊：
--
影响因子：
--
作者：
C. Sina;O. Gavrilova;M. Förster;A. Till;S. Derer;F. Hildebrand;Björn Raabe;A. Chalaris;J. Sch
通讯作者：
C. Sina;O. Gavrilova;M. Förster;A. Till;S. Derer;F. Hildebrand;Björn Raabe;A. Chalaris;J. Sch
影响因子：
4.8
作者：
Brown, AJ;Goldsworthy, SM;Dowell, SJ
通讯作者：
Dowell, SJ
DOI：
10.1073/pnas.2637002100
发表时间：
2004-01-27
影响因子：
11.1
作者：
Xiong, YM;Miyamoto, N;Yanagisawa, M
通讯作者：
Yanagisawa, M