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Tauroursodeoxycholic acid protects bile acid homeostasis under inflammatory conditions and dampens Crohn’s disease-like ileitis

Lien Van den Bossche, Daniel Borsboom, Sarah Devriese, Sophie Van Welden UGent, Tom Holvoet UGent, Lindsey Devisscher UGent, Pieter Hindryckx UGent, Martine De Vos UGent and Debby Laukens UGent (2017) LABORATORY INVESTIGATION. 97(5). p.519-529
abstract
Bile acids regulate the expression of intestinal bile acid transporters and are natural ligands for nuclear receptors controlling inflammation. Accumulating evidence suggests that signaling through these receptors is impaired in inflammatory bowel disease. We investigated whether tauroursodeoxycholic acid (TUDCA), a secondary bile acid with cytoprotective properties, regulates ileal nuclear receptor and bile acid transporter expression and assessed its therapeutic potential in an experimental model of Crohn's disease (CD). Gene expression of the nuclear receptors farnesoid X receptor, pregnane X receptor and vitamin D receptor and the bile acid transporters apical sodium-dependent bile acid transporter and organic solute transporter a and (3 was analyzed in Caco-2 cell monolayers exposed to tumor necrosis factor (TNF)alpha, in ileal tissue of TNF Delta ARE/WT mice and in inflamed ilea) biopsies from CD patients by quantitative real-time polymerase chain reaction. TNF Delta ARE/WT mice and wild-type littermates were treated with TUDCA or placebo for 11 weeks and ileal histopathology and expression of the aforementioned genes were determined. Exposing Caco-2 cell monolayers to TNFa impaired the mRNA expression of nuclear receptors and bile acid transporters, whereas co-incubation with TUDCA antagonized their downregulation. TNF Delta ARE/WT mice displayed altered ileal bile acid homeostasis that mimicked the situation in human CD ileitis. Administration of TUDCA attenuated ileitis and alleviated the downregulation of nuclear receptors and bile acid transporters in these mice. These results show that TUDCA protects bile acid homeostasis under inflammatory conditions and suppresses CD-like ileitis. Together with previous observations showing similar efficacy in experimental colitis, we conclude that TUDCA could be a promising therapeutic agent for inflammatory bowel disease, warranting a clinical trial.
Please use this url to cite or link to this publication:
author
organization
year
type
journalArticle (original)
publication status
published
subject
keyword
PREGNANE-X-RECEPTOR, VITAMIN-D-RECEPTOR, ALPHA-OST-BETA, CYTOKINE-DEPENDENT REGULATION, INTESTINAL EPITHELIAL-CELLS, BOWEL-DISEASE, URSODEOXYCHOLIC ACID, TRANSPORTER GENE, MEDIATED REPRESSION, MESSENGER-RNA
journal title
LABORATORY INVESTIGATION
Lab. Invest.
volume
97
issue
5
pages
519 - 529
Web of Science type
Article
Web of Science id
000400229900003
ISSN
0023-6837
DOI
10.1038/labinvest.2017.6
language
English
UGent publication?
yes
classification
A1
copyright statement
I have transferred the copyright for this publication to the publisher
id
8502457
handle
http://hdl.handle.net/1854/LU-8502457
date created
2017-01-17 08:50:43
date last changed
2017-10-17 11:53:05
@article{8502457,
  abstract     = {Bile acids regulate the expression of intestinal bile acid transporters and are natural ligands for nuclear receptors controlling inflammation. Accumulating evidence suggests that signaling through these receptors is impaired in inflammatory bowel disease. We investigated whether tauroursodeoxycholic acid (TUDCA), a secondary bile acid with cytoprotective properties, regulates ileal nuclear receptor and bile acid transporter expression and assessed its therapeutic potential in an experimental model of Crohn's disease (CD). Gene expression of the nuclear receptors farnesoid X receptor, pregnane X receptor and vitamin D receptor and the bile acid transporters apical sodium-dependent bile acid transporter and organic solute transporter a and (3 was analyzed in Caco-2 cell monolayers exposed to tumor necrosis factor (TNF)alpha, in ileal tissue of TNF Delta ARE/WT mice and in inflamed ilea) biopsies from CD patients by quantitative real-time polymerase chain reaction. TNF Delta ARE/WT mice and wild-type littermates were treated with TUDCA or placebo for 11 weeks and ileal histopathology and expression of the aforementioned genes were determined. Exposing Caco-2 cell monolayers to TNFa impaired the mRNA expression of nuclear receptors and bile acid transporters, whereas co-incubation with TUDCA antagonized their downregulation. TNF Delta ARE/WT mice displayed altered ileal bile acid homeostasis that mimicked the situation in human CD ileitis. Administration of TUDCA attenuated ileitis and alleviated the downregulation of nuclear receptors and bile acid transporters in these mice. These results show that TUDCA protects bile acid homeostasis under inflammatory conditions and suppresses CD-like ileitis. Together with previous observations showing similar efficacy in experimental colitis, we conclude that TUDCA could be a promising therapeutic agent for inflammatory bowel disease, warranting a clinical trial.},
  author       = {Van den Bossche, Lien and Borsboom, Daniel and Devriese, Sarah and Van Welden, Sophie and Holvoet, Tom and Devisscher, Lindsey and Hindryckx, Pieter and De Vos, Martine and Laukens, Debby},
  issn         = {0023-6837},
  journal      = {LABORATORY INVESTIGATION},
  keyword      = {PREGNANE-X-RECEPTOR,VITAMIN-D-RECEPTOR,ALPHA-OST-BETA,CYTOKINE-DEPENDENT REGULATION,INTESTINAL EPITHELIAL-CELLS,BOWEL-DISEASE,URSODEOXYCHOLIC ACID,TRANSPORTER GENE,MEDIATED REPRESSION,MESSENGER-RNA},
  language     = {eng},
  number       = {5},
  pages        = {519--529},
  title        = {Tauroursodeoxycholic acid protects bile acid homeostasis under inflammatory conditions and dampens Crohn{\textquoteright}s disease-like ileitis},
  url          = {http://dx.doi.org/10.1038/labinvest.2017.6},
  volume       = {97},
  year         = {2017},
}

Chicago
Van den Bossche, Lien, Daniel Borsboom, Sarah Devriese, Sophie Van Welden, Tom Holvoet, Lindsey Devisscher, Pieter Hindryckx, Martine De Vos, and Debby Laukens. 2017. “Tauroursodeoxycholic Acid Protects Bile Acid Homeostasis Under Inflammatory Conditions and Dampens Crohn’s Disease-like Ileitis.” Laboratory Investigation 97 (5): 519–529.
APA
Van den Bossche, L., Borsboom, D., Devriese, S., Van Welden, S., Holvoet, T., Devisscher, L., Hindryckx, P., et al. (2017). Tauroursodeoxycholic acid protects bile acid homeostasis under inflammatory conditions and dampens Crohn’s disease-like ileitis. LABORATORY INVESTIGATION, 97(5), 519–529.
Vancouver
1.
Van den Bossche L, Borsboom D, Devriese S, Van Welden S, Holvoet T, Devisscher L, et al. Tauroursodeoxycholic acid protects bile acid homeostasis under inflammatory conditions and dampens Crohn’s disease-like ileitis. LABORATORY INVESTIGATION. 2017;97(5):519–29.
MLA
Van den Bossche, Lien, Daniel Borsboom, Sarah Devriese, et al. “Tauroursodeoxycholic Acid Protects Bile Acid Homeostasis Under Inflammatory Conditions and Dampens Crohn’s Disease-like Ileitis.” LABORATORY INVESTIGATION 97.5 (2017): 519–529. Print.