Bile acids and their receptors: modulators and therapeutic targets in liver inflammation

被引：85

作者：

Bertolini, Anna ^{[1
,2
]}

Fiorotto, Romina ^{[1
]}

Strazzabosco, Mario ^{[1
]}

机构：

[1] Yale Sch Med, Yale Liver Ctr, Sect Digest Dis, POB 208019, New Haven, CT 06520 USA

[2] Univ Med Ctr Groningen, Dept Pediat, Sect Mol Metab & Nutr, Groningen, Netherlands

来源：

SEMINARS IN IMMUNOPATHOLOGY | 2022年 / 44卷 / 04期

基金：

美国国家卫生研究院;

关键词：

Bile acids; Bile acid receptors; Inflammation; Liver; Cholestasis; FXR; TGR5; FARNESOID-X-RECEPTOR; NF-KAPPA-B; PRIMARY BILIARY CHOLANGITIS; INDUCED HEPATIC INFLAMMATION; TUMOR-NECROSIS-FACTOR; CHOLESTATIC LIVER; NUCLEAR RECEPTORS; OBETICHOLIC ACID; URSODEOXYCHOLIC ACID; EPITHELIAL-CELLS;

D O I：

10.1007/s00281-022-00935-7

中图分类号：

R392 [医学免疫学]; Q939.91 [免疫学];

学科分类号：

100102 ;

摘要：

Bile acids participate in the intestinal emulsion, digestion, and absorption of lipids and fat-soluble vitamins. When present in high concentrations, as in cholestatic liver diseases, bile acids can damage cells and cause inflammation. After the discovery of bile acids receptors about two decades ago, bile acids are considered signaling molecules. Besides regulating bile acid, xenobiotic, and nutrient metabolism, bile acids and their receptors have shown immunomodulatory properties and have been proposed as therapeutic targets for inflammatory diseases of the liver. This review focuses on bile acid-related signaling pathways that affect inflammation in the liver and provides an overview of the preclinical and clinical applications of modulators of these pathways for the treatment of cholestatic and autoimmune liver diseases.

引用

页码：547 / 564

页数：18

共 210 条

[1] Blocking Sodium-Taurocholate Cotransporting Polypeptide Stimulates Biliary Cholesterol and Phospholipid Secretion in Mice [J].

Abbing, Reinout L. P. Roscam ;

Slijepcevic, Davor ;

Donkers, Joanne M. ;

Havinga, Rick ;

Duijst, Suzanne ;

Paulusma, Coen C. ;

Kuiper, Johan ;

Kuipers, Folkert ;

Groen, Albert K. ;

Elferink, Ronald P. J. Oude ;

van de Graaf, Stan F. J. .

HEPATOLOGY, 2020, 71 (01) :247-258

[2] Activation of necroptosis in human and experimental cholestasis [J].

Afonso, Marta B. ;

Rodrigues, Pedro M. ;

Simao, Andre L. ;

Ofengeim, Dimitry ;

Carvalho, Tania ;

Amaral, Joana D. ;

Gaspar, Maria M. ;

Cortez-Pinto, Helena ;

Castro, Rui E. ;

Yuan, Junying ;

Rodrigues, Cecilia M. P. .

CELL DEATH & DISEASE, 2016, 7 :e2390-e2390

[3] The TGR5 receptor mediates bile acid-induced itch and analgesia [J].

Alemi, Farzad ;

Kwon, Edwin ;

Poole, Daniel P. ;

Lieu, TinaMarie ;

Lyo, Victoria ;

Cattaruzza, Fiore ;

Cevikbas, Ferda ;

Steinhoff, Martin ;

Nassini, Romina ;

Materazzi, Serena ;

Guerrero-Alba, Raquel ;

Valdez-Morales, Eduardo ;

Cottrell, Graeme S. ;

Schoonjans, Kristina ;

Geppetti, Pierangelo ;

Vanner, Stephen J. ;

Bunnett, Nigel W. ;

Corvera, Carlos U. .

JOURNAL OF CLINICAL INVESTIGATION, 2013, 123 (04) :1513-1530

[4] Bile Acids Induce Inflammatory Genes in Hepatocytes A Novel Mechanism of Inflammation during Obstructive Cholestasis [J].

Allen, Katryn ;

Jaeschke, Hartmut ;

Copple, Bryan L. .

AMERICAN JOURNAL OF PATHOLOGY, 2011, 178 (01) :175-186

[5] BILE ACID-INDUCED LIVER TOXICITY - RELATION TO THE HYDROPHOBICHYDROPHILIC BALANCE OF BILE-ACIDS [J].

ATTILI, AF ;

ANGELICO, M ;

CANTAFORA, A ;

ALVARO, D ;

CAPOCACCIA, L .

MEDICAL HYPOTHESES, 1986, 19 (01) :57-69

[6] Inhibition of intestinal bile acid absorption improves cholestatic liver and bile duct injury in a mouse model of sclerosing cholangitis [J].

Baghdasaryan, Anna ;

Fuchs, Claudia D. ;

Oesterreicher, Christoph H. ;

Lemberger, Ursula J. ;

Halilbasic, Emina ;

Pahlman, Ingrid ;

Graffner, Hans ;

Krones, Elisabeth ;

Fickert, Peter ;

Wahlstrom, Annika ;

Stahlman, Marcus ;

Paumgartner, Gustav ;

Marschall, Hanns-Ulrich ;

Trauner, Michael .

JOURNAL OF HEPATOLOGY, 2016, 64 (03) :674-681

[7] Dual Farnesoid X Receptor/TGR5 Agonist INT-767 Reduces Liver Injury in the Mdr2-/- (Abcb4-/-) Mouse Cholangiopathy Model by Promoting Biliary HCO3- Output [J].

Baghdasaryan, Anna ;

Claudel, Thierry ;

Gumhold, Judith ;

Silbert, Dagmar ;

Adorini, Luciano ;

Roda, Aldo ;

Vecchiotti, Stefania ;

Gonzalez, Frank J. ;

Schoonjans, Kristina ;

Strazzabosco, Mario ;

Fickert, Peter ;

Trauner, Michael .

HEPATOLOGY, 2011, 54 (04) :1303-1312

[8] The acute phase response is associated with retinoid X receptor repression in rodent liver [J].

Beigneux, AP ;

Moser, AH ;

Shigenaga, JK ;

Grunfeld, C ;

Feingold, KR .

JOURNAL OF BIOLOGICAL CHEMISTRY, 2000, 275 (21) :16390-16399

[9]

Benedetti A, 1997, HEPATOLOGY, V26, P9

[10] Bile acids with differing hydrophilic-hydrophobic properties do not influence cytokine production by human monocytes and murine Kupffer cells [J].

Bergamini, A ;

Dini, L ;

Baiocchi, L ;

Cappannoli, L ;

Falasca, L ;

Bolacchi, F ;

Capozzi, M ;

Faggioli, E ;

Nistri, A ;

Salanitro, A ;

Ventura, L ;

Rocchi, G ;

Angelico, M .

HEPATOLOGY, 1997, 25 (04) :927-933

← 1 2 3 4 5 6 7 8 9 10 →