Bile Acids Elevated in Chronic Periaortitis Could Activate Farnesoid-X-Receptor to Suppress IL-6 Production by Macrophages

doi:10.3389/fimmu.2021.632864

科研成果详情

题名	Bile Acids Elevated in Chronic Periaortitis Could Activate Farnesoid-X-Receptor to Suppress IL-6 Production by Macrophages
作者	Cao, Shan 1; Meng, Xinyu 1; Li, Yixuan 1; Sun, Li 2; Jiang, Lindi 3; Xuan, Hanqing 4; Chen, Xiaoxiang 1
发表日期	2021-04-22
发表期刊	FRONTIERS IN IMMUNOLOGY 影响因子和分区
语种	英语
原始文献类型	Article
关键词	bile acid farnesoid-x-receptor IL-6 chronic periaortitis macrophages
其他关键词	EFFICACY
摘要	Chronic periaortitis (CP) is a rare autoimmune disease without effective treatment. By analyzing the serum bile acid spectrum in 28 CP patients with the ultra-performance liquid chromatography-tandem mass spectrometry, we found that the bile acids were significantly altered in CP patients, with significant increases in chenodeoxycholic acid (CDCA) and glycochenodeoxycholic acid (GCDCA) and decrease in deoxycholic acid (DCA). Signaling pathway enrichment analysis from the RNA sequencing results suggested that the altered gene sets in PBMC of CP patients were associated with bile acid metabolism. Furthermore, we found that pathological concentration of CDCA could significantly inhibited IL-6 expression in RAW 264.7 cells after LPS stimulation. Since CDCA is a well-known natural high-affinity ligand for the bile acid receptor farnesoid-x-receptor (FXR) while GW4064 is the synthetic specific agonist of this receptor, we then revealed that GW4064 significantly decreased IL-6 expression in RAW 264.7 cells and bone marrow-derived macrophages but not in FXR-/- macrophages upon LPS stimulation. The western blot results with the anti-FXR antibody showed significantly increased expression in the nuclear proportion, suggesting that FXR agonist promoted the transportation of FXR into the nucleus but did not increase the FXR expression in macrophages. Dual-luciferase report assay and ChIP assay demonstrated that upon activation, FXR could directly bind to the promoter site of IL-6, leading to the decreased expression of IL-6. Thus, bile acids, especially CDCA, may operate to damp inflammation via FXR-mediated downregulation of IL-6 in mononuclear cells and provide a protective mechanism for CP patients.
资助项目	National Science Foundation of ChinaNational Natural Science Foundation of China (NSFC) [81771729, 81971534]
出版者	FRONTIERS MEDIA SA
出版地	LAUSANNE
ISSN	1664-3224
卷号	12 页码:632864
DOI	10.3389/fimmu.2021.632864
页数	12
WOS类目	Immunology
WOS研究方向	Immunology
WOS记录号	WOS:000647452400001
收录类别	SCIE ; PUBMED ; SCOPUS
URL	查看原文
PubMed ID	33968024
PMC记录号	PMC8100322
SCOPUSEID	2-s2.0-85105392533
通讯作者地址	[Chen, Xiaoxiang]Department of Rheumatology,Ren Ji Hospital,Shanghai Jiao Tong University School of Medicine,Shanghai,China ; [Xuan, Hanqing]Department of Urology,Ren Ji Hospital,Shanghai Jiaotong University School of Medicine,Shanghai,China
Scopus学科分类	Immunology and Allergy;Immunology
引用统计	被引频次：3[WOS] [WOS记录] [WOS相关记录]
文献类型	期刊论文
条目标识符	https://kms.wmu.edu.cn/handle/3ETUA0LF/6282
专题	附属第一医院_风湿免疫科
通讯作者	Xuan, Hanqing; Chen, Xiaoxiang
作者单位	1.Department of Rheumatology,Ren Ji Hospital,Shanghai Jiao Tong University School of Medicine,Shanghai,China; 2.Department of Rheumatology,Hospital of Wenzhou Medical University,Wenzhou,China; 3.Department of Rheumatology,Zhongshan Hospital,Fudan University,Shanghai,China; 4.Department of Urology,Ren Ji Hospital,Shanghai Jiaotong University School of Medicine,Shanghai,China
推荐引用方式 GB/T 7714	Cao, Shan,Meng, Xinyu,Li, Yixuan,et al. Bile Acids Elevated in Chronic Periaortitis Could Activate Farnesoid-X-Receptor to Suppress IL-6 Production by Macrophages[J]. FRONTIERS IN IMMUNOLOGY,2021,12:632864.
APA	Cao, Shan., Meng, Xinyu., Li, Yixuan., Sun, Li., Jiang, Lindi., ... & Chen, Xiaoxiang. (2021). Bile Acids Elevated in Chronic Periaortitis Could Activate Farnesoid-X-Receptor to Suppress IL-6 Production by Macrophages. FRONTIERS IN IMMUNOLOGY, 12, 632864.
MLA	Cao, Shan,et al."Bile Acids Elevated in Chronic Periaortitis Could Activate Farnesoid-X-Receptor to Suppress IL-6 Production by Macrophages".FRONTIERS IN IMMUNOLOGY 12(2021):632864.