Please use this identifier to cite or link to this item: https://doi.org/10.1371/journal.pone.0025637
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dc.titleThe bile acid receptor GPBAR-1 (TGR5) modulates integrity of intestinal barrier and immune response to experimental colitis
dc.contributor.authorCipriani S.
dc.contributor.authorMencarelli A.
dc.contributor.authorChini M.G.
dc.contributor.authorDistrutti E.
dc.contributor.authorRenga B.
dc.contributor.authorBifulco G.
dc.contributor.authorBaldelli F.
dc.contributor.authorDonini A.
dc.contributor.authorFiorucci S.
dc.date.accessioned2019-11-11T08:36:54Z
dc.date.available2019-11-11T08:36:54Z
dc.date.issued2011
dc.identifier.citationCipriani 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
dc.identifier.issn19326203
dc.identifier.urihttps://scholarbank.nus.edu.sg/handle/10635/162026
dc.description.abstractBackground: 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.
dc.rightsAttribution 4.0 International
dc.rights.urihttp://creativecommons.org/licenses/by/4.0/
dc.sourceUnpaywall 20191101
dc.subjectCD14 antigen
dc.subjectciprofloxacin
dc.subjectcyclic AMP
dc.subjectgap junction protein
dc.subjectoleanolic acid
dc.subjecttoll like receptor 4
dc.subjecttrinitrobenzenesulfonic acid
dc.subjecttumor necrosis factor alpha
dc.subjectunclassified drug
dc.subjectzonulin 1
dc.subjectcholera toxin
dc.subjectciprofloxacin
dc.subjectG protein coupled receptor
dc.subjectGpbar1 protein, mouse
dc.subjectligand
dc.subjectzonulin
dc.subjectadult
dc.subjectanimal cell
dc.subjectanimal experiment
dc.subjectanimal model
dc.subjectanimal tissue
dc.subjectantiinflammatory activity
dc.subjectarticle
dc.subjectcell isolation
dc.subjectcell junction
dc.subjectcell structure
dc.subjectcellular distribution
dc.subjectcolitis
dc.subjectcontrolled study
dc.subjectCrohn disease
dc.subjectdisease severity
dc.subjectdose response
dc.subjectdrug dose comparison
dc.subjectdrug mechanism
dc.subjectdrug structure
dc.subjectfemale
dc.subjectflow cytometry
dc.subjectG protein coupled bile acid receptor 1 gene
dc.subjectgene deletion
dc.subjectgene expression regulation
dc.subjectgene function
dc.subjecthomeostasis
dc.subjecthuman
dc.subjecthuman tissue
dc.subjectimmune response
dc.subjectimmunomodulation
dc.subjectimmunoregulation
dc.subjectintestine mucosa permeability
dc.subjectmale
dc.subjectmolecular docking
dc.subjectmucous cell
dc.subjectnonhuman
dc.subjectreceptor gene
dc.subjectscreening test
dc.subjectwild type
dc.subjectanimal
dc.subjectchemically induced disorder
dc.subjectcolitis
dc.subjectimmunity
dc.subjectimmunology
dc.subjectintestine mucosa
dc.subjectmouse
dc.subjectmouse mutant
dc.subjectpathology
dc.subjectpermeability
dc.subjectphysiology
dc.subjecttight junction
dc.subjectMus
dc.subjectRodentia
dc.subjectAnimals
dc.subjectCholera Toxin
dc.subjectCiprofloxacin
dc.subjectColitis
dc.subjectImmunity
dc.subjectIntestinal Mucosa
dc.subjectLigands
dc.subjectMice
dc.subjectMice, Knockout
dc.subjectPermeability
dc.subjectReceptors, G-Protein-Coupled
dc.subjectTight Junctions
dc.typeArticle
dc.contributor.departmentDEAN'S OFFICE (DUKE-NUS MEDICAL SCHOOL)
dc.contributor.departmentDUKE-NUS MEDICAL SCHOOL
dc.description.doi10.1371/journal.pone.0025637
dc.description.sourcetitlePLoS ONE
dc.description.volume6
dc.description.issue10
dc.description.pagee25637
dc.published.statePublished
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