Please use this identifier to cite or link to this item: https://doi.org/10.1371/journal.pone.0025637
Title: The bile acid receptor GPBAR-1 (TGR5) modulates integrity of intestinal barrier and immune response to experimental colitis
Authors: Cipriani S.
Mencarelli A. 
Chini M.G.
Distrutti E.
Renga B.
Bifulco G.
Baldelli F.
Donini A.
Fiorucci S.
Keywords: CD14 antigen
ciprofloxacin
cyclic AMP
gap junction protein
oleanolic acid
toll like receptor 4
trinitrobenzenesulfonic acid
tumor necrosis factor alpha
unclassified drug
zonulin 1
cholera toxin
ciprofloxacin
G protein coupled receptor
Gpbar1 protein, mouse
ligand
zonulin
adult
animal cell
animal experiment
animal model
animal tissue
antiinflammatory activity
article
cell isolation
cell junction
cell structure
cellular distribution
colitis
controlled study
Crohn disease
disease severity
dose response
drug dose comparison
drug mechanism
drug structure
female
flow cytometry
G protein coupled bile acid receptor 1 gene
gene deletion
gene expression regulation
gene function
homeostasis
human
human tissue
immune response
immunomodulation
immunoregulation
intestine mucosa permeability
male
molecular docking
mucous cell
nonhuman
receptor gene
screening test
wild type
animal
chemically induced disorder
colitis
immunity
immunology
intestine mucosa
mouse
mouse mutant
pathology
permeability
physiology
tight junction
Mus
Rodentia
Animals
Cholera Toxin
Ciprofloxacin
Colitis
Immunity
Intestinal Mucosa
Ligands
Mice
Mice, Knockout
Permeability
Receptors, G-Protein-Coupled
Tight Junctions
Issue Date: 2011
Citation: Cipriani S., Mencarelli A., Chini M.G., Distrutti E., Renga B., Bifulco G., Baldelli F., Donini A., Fiorucci S. (2011). The bile acid receptor GPBAR-1 (TGR5) modulates integrity of intestinal barrier and immune response to experimental colitis. PLoS ONE 6 (10) : e25637. ScholarBank@NUS Repository. https://doi.org/10.1371/journal.pone.0025637
Rights: Attribution 4.0 International
Abstract: Background: GP-BAR1, a member G protein coupled receptor superfamily, is a cell surface bile acid-activated receptor highly expressed in the ileum and colon. In monocytes, ligation of GP-BAR1 by secondary bile acids results in a cAMP-dependent attenuation of cytokine generation. Aims: To investigate the role GP-BAR1 in regulating intestinal homeostasis and inflammation-driven immune dysfunction in rodent models of colitis. Methods: Colitis was induced in wild type and GP-BAR1 -/- mice by DSS and TNBS administration. Potential GP-BAR1 agonists were identified by in silico screening and computational docking studies. Results: GP-BAR1 -/- mice develop an abnormal morphology of colonic mucous cells and an altered molecular architecture of epithelial tight junctions with increased expression and abnormal subcellular distribution of zonulin 1 resulting in increased intestinal permeability and susceptibility to develop severe colitis in response to DSS at early stage of life. By in silico screening and docking studies we identified ciprofloxacin as a GP-BAR1 ligand. In monocytes, ciprofloxacin increases cAMP concentrations and attenuates TNF? release induced by TLR4 ligation in a GP-BAR1 dependent manner. Treating mice rendered colitic by TNBS with ciprofloxacin and oleanolic acid, a well characterized GP-BAR1 ligand, abrogates signs and symptoms of colitis. Colonic expression of GP-BAR1 mRNA increases in rodent models of colitis and tissues from Crohn's disease patients. Flow cytometry analysis demonstrates that ?90% of CD14+ cells isolated from the lamina propria of TNBS-treated mice stained positively for GP-BAR1. Conclusions: GP-BAR1 regulates intestinal barrier structure. Its expression increases in rodent models of colitis and Crohn's disease. Ciprofloxacin is a GP-BAR1 ligand. © 2011 Cipriani et al.
Source Title: PLoS ONE
URI: https://scholarbank.nus.edu.sg/handle/10635/162026
ISSN: 19326203
DOI: 10.1371/journal.pone.0025637
Rights: Attribution 4.0 International
Appears in Collections:Elements
Staff Publications

Show full item record
Files in This Item:
File Description SizeFormatAccess SettingsVersion 
10_1371_journal_pone_0025637.pdf5.9 MBAdobe PDF

OPEN

NoneView/Download

Google ScholarTM

Check

Altmetric


This item is licensed under a Creative Commons License Creative Commons