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

(2017) LABORATORY INVESTIGATION. 97(5). p.519-529
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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.
Keywords
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

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Citation

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MLA
Van den Bossche, Lien 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.
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.
Chicago author-date
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.
Chicago author-date (all authors)
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.
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.
IEEE
[1]
L. Van den Bossche et al., “Tauroursodeoxycholic acid protects bile acid homeostasis under inflammatory conditions and dampens Crohn’s disease-like ileitis,” LABORATORY INVESTIGATION, vol. 97, no. 5, pp. 519–529, 2017.
@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},
  keywords     = {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’s disease-like ileitis},
  url          = {http://dx.doi.org/10.1038/labinvest.2017.6},
  volume       = {97},
  year         = {2017},
}

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