Bile Acids Elevated in Chronic Periaortitis Could Activate Farnesoid-X-Receptor to Suppress IL-6 Production by Macrophages
被引:15
作者:
Cao, Shan
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机构:
Shanghai Jiao Tong Univ, Ren Ji Hosp, Dept Rheumatol, Sch Med, Shanghai, Peoples R ChinaShanghai Jiao Tong Univ, Ren Ji Hosp, Dept Rheumatol, Sch Med, Shanghai, Peoples R China
Cao, Shan
[1
]
Meng, Xinyu
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机构:
Shanghai Jiao Tong Univ, Ren Ji Hosp, Dept Rheumatol, Sch Med, Shanghai, Peoples R ChinaShanghai Jiao Tong Univ, Ren Ji Hosp, Dept Rheumatol, Sch Med, Shanghai, Peoples R China
Meng, Xinyu
[1
]
Li, Yixuan
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机构:
Shanghai Jiao Tong Univ, Ren Ji Hosp, Dept Rheumatol, Sch Med, Shanghai, Peoples R ChinaShanghai Jiao Tong Univ, Ren Ji Hosp, Dept Rheumatol, Sch Med, Shanghai, Peoples R China
Li, Yixuan
[1
]
Sun, Li
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机构:
Wenzhou Med Univ, Dept Rheumatol, Affiliated Hosp 1, Wenzhou, Peoples R ChinaShanghai Jiao Tong Univ, Ren Ji Hosp, Dept Rheumatol, Sch Med, Shanghai, Peoples R China
Sun, Li
[2
]
Jiang, Lindi
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机构:
Fudan Univ, Zhongshan Hosp, Dept Rheumatol, Shanghai, Peoples R ChinaShanghai Jiao Tong Univ, Ren Ji Hosp, Dept Rheumatol, Sch Med, Shanghai, Peoples R China
Jiang, Lindi
[3
]
Xuan, Hanqing
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h-index: 0
机构:
Shanghai Jiao Tong Univ, Ren Ji Hosp, Dept Urol, Sch Med, Shanghai, Peoples R ChinaShanghai Jiao Tong Univ, Ren Ji Hosp, Dept Rheumatol, Sch Med, Shanghai, Peoples R China
Xuan, Hanqing
[4
]
Chen, Xiaoxiang
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机构:
Shanghai Jiao Tong Univ, Ren Ji Hosp, Dept Rheumatol, Sch Med, Shanghai, Peoples R ChinaShanghai Jiao Tong Univ, Ren Ji Hosp, Dept Rheumatol, Sch Med, Shanghai, Peoples R China
Chen, Xiaoxiang
[1
]
机构:
[1] Shanghai Jiao Tong Univ, Ren Ji Hosp, Dept Rheumatol, Sch Med, Shanghai, Peoples R China
[2] Wenzhou Med Univ, Dept Rheumatol, Affiliated Hosp 1, Wenzhou, Peoples R China
[3] Fudan Univ, Zhongshan Hosp, Dept Rheumatol, Shanghai, Peoples R China
[4] Shanghai Jiao Tong Univ, Ren Ji Hosp, Dept Urol, Sch Med, Shanghai, Peoples R China
来源:
FRONTIERS IN IMMUNOLOGY
|
2021年
/
12卷
基金:
美国国家科学基金会;
关键词:
bile acid;
farnesoid-x-receptor;
IL-6;
chronic periaortitis;
macrophages;
EFFICACY;
D O I:
10.3389/fimmu.2021.632864
中图分类号:
R392 [医学免疫学];
Q939.91 [免疫学];
学科分类号:
100102 ;
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.
机构:
Univ Calif Los Angeles, Howard Hughes Med Inst, Dept Pathol & Lab Med, Los Angeles, CA 90095 USAUniv Calif Los Angeles, Howard Hughes Med Inst, Dept Pathol & Lab Med, Los Angeles, CA 90095 USA
Calkin, Anna C.
Tontonoz, Peter
论文数: 0引用数: 0
h-index: 0
机构:
Univ Calif Los Angeles, Howard Hughes Med Inst, Dept Pathol & Lab Med, Los Angeles, CA 90095 USAUniv Calif Los Angeles, Howard Hughes Med Inst, Dept Pathol & Lab Med, Los Angeles, CA 90095 USA
机构:
Univ Milano Bicocca, Dept Med & Surg, Div Gastroenterol, Monza, Italy
Univ Milano Bicocca, Dept Med & Surg, Ctr Autoimmune Liver Dis, Monza, Italy
San Gerardo Hosp, European Reference Network Hepatol Dis ERN RARE L, Monza, ItalyUniv Milano Bicocca, Dept Med & Surg, Div Gastroenterol, Monza, Italy
Luca, Martina
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机构:
Cristoferi, Laura
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Ronca, Vincenzo
Mancuso, Clara
论文数: 0引用数: 0
h-index: 0
机构:
Univ Milano Bicocca, Dept Med & Surg, Div Gastroenterol, Monza, Italy
Univ Milano Bicocca, Dept Med & Surg, Ctr Autoimmune Liver Dis, Monza, Italy
San Gerardo Hosp, European Reference Network Hepatol Dis ERN RARE L, Monza, ItalyUniv Milano Bicocca, Dept Med & Surg, Div Gastroenterol, Monza, Italy
Mancuso, Clara
Milani, Chiara
论文数: 0引用数: 0
h-index: 0
机构:
Univ Milano Bicocca, Dept Med & Surg, Div Gastroenterol, Monza, Italy
Univ Milano Bicocca, Dept Med & Surg, Ctr Autoimmune Liver Dis, Monza, Italy
San Gerardo Hosp, European Reference Network Hepatol Dis ERN RARE L, Monza, ItalyUniv Milano Bicocca, Dept Med & Surg, Div Gastroenterol, Monza, Italy
Milani, Chiara
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机构:
D'Amato, Daphne
O'Donnell, Sarah Elizabeth
论文数: 0引用数: 0
h-index: 0
机构:
Univ Milano Bicocca, Dept Med & Surg, Div Gastroenterol, Monza, Italy
Univ Milano Bicocca, Dept Med & Surg, Ctr Autoimmune Liver Dis, Monza, Italy
San Gerardo Hosp, European Reference Network Hepatol Dis ERN RARE L, Monza, ItalyUniv Milano Bicocca, Dept Med & Surg, Div Gastroenterol, Monza, Italy
O'Donnell, Sarah Elizabeth
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机构:
Carbone, Marco
Invernizzi, Pietro
论文数: 0引用数: 0
h-index: 0
机构:
Univ Milano Bicocca, Dept Med & Surg, Div Gastroenterol, Monza, Italy
Univ Milano Bicocca, Dept Med & Surg, Ctr Autoimmune Liver Dis, Monza, Italy
San Gerardo Hosp, European Reference Network Hepatol Dis ERN RARE L, Monza, ItalyUniv Milano Bicocca, Dept Med & Surg, Div Gastroenterol, Monza, Italy
机构:
Univ Calif Los Angeles, Howard Hughes Med Inst, Dept Pathol & Lab Med, Los Angeles, CA 90095 USAUniv Calif Los Angeles, Howard Hughes Med Inst, Dept Pathol & Lab Med, Los Angeles, CA 90095 USA
Calkin, Anna C.
Tontonoz, Peter
论文数: 0引用数: 0
h-index: 0
机构:
Univ Calif Los Angeles, Howard Hughes Med Inst, Dept Pathol & Lab Med, Los Angeles, CA 90095 USAUniv Calif Los Angeles, Howard Hughes Med Inst, Dept Pathol & Lab Med, Los Angeles, CA 90095 USA
机构:
Univ Milano Bicocca, Dept Med & Surg, Div Gastroenterol, Monza, Italy
Univ Milano Bicocca, Dept Med & Surg, Ctr Autoimmune Liver Dis, Monza, Italy
San Gerardo Hosp, European Reference Network Hepatol Dis ERN RARE L, Monza, ItalyUniv Milano Bicocca, Dept Med & Surg, Div Gastroenterol, Monza, Italy
Luca, Martina
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机构:
Cristoferi, Laura
论文数: 引用数:
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机构:
Ronca, Vincenzo
Mancuso, Clara
论文数: 0引用数: 0
h-index: 0
机构:
Univ Milano Bicocca, Dept Med & Surg, Div Gastroenterol, Monza, Italy
Univ Milano Bicocca, Dept Med & Surg, Ctr Autoimmune Liver Dis, Monza, Italy
San Gerardo Hosp, European Reference Network Hepatol Dis ERN RARE L, Monza, ItalyUniv Milano Bicocca, Dept Med & Surg, Div Gastroenterol, Monza, Italy
Mancuso, Clara
Milani, Chiara
论文数: 0引用数: 0
h-index: 0
机构:
Univ Milano Bicocca, Dept Med & Surg, Div Gastroenterol, Monza, Italy
Univ Milano Bicocca, Dept Med & Surg, Ctr Autoimmune Liver Dis, Monza, Italy
San Gerardo Hosp, European Reference Network Hepatol Dis ERN RARE L, Monza, ItalyUniv Milano Bicocca, Dept Med & Surg, Div Gastroenterol, Monza, Italy
Milani, Chiara
论文数: 引用数:
h-index:
机构:
D'Amato, Daphne
O'Donnell, Sarah Elizabeth
论文数: 0引用数: 0
h-index: 0
机构:
Univ Milano Bicocca, Dept Med & Surg, Div Gastroenterol, Monza, Italy
Univ Milano Bicocca, Dept Med & Surg, Ctr Autoimmune Liver Dis, Monza, Italy
San Gerardo Hosp, European Reference Network Hepatol Dis ERN RARE L, Monza, ItalyUniv Milano Bicocca, Dept Med & Surg, Div Gastroenterol, Monza, Italy
O'Donnell, Sarah Elizabeth
论文数: 引用数:
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机构:
Carbone, Marco
Invernizzi, Pietro
论文数: 0引用数: 0
h-index: 0
机构:
Univ Milano Bicocca, Dept Med & Surg, Div Gastroenterol, Monza, Italy
Univ Milano Bicocca, Dept Med & Surg, Ctr Autoimmune Liver Dis, Monza, Italy
San Gerardo Hosp, European Reference Network Hepatol Dis ERN RARE L, Monza, ItalyUniv Milano Bicocca, Dept Med & Surg, Div Gastroenterol, Monza, Italy