| http://purl.uniprot.org/citations/24278446 | http://www.w3.org/1999/02/22-rdf-syntax-ns#type | http://purl.uniprot.org/core/Journal_Citation |
| http://purl.uniprot.org/citations/24278446 | http://www.w3.org/2000/01/rdf-schema#comment | "C. difficile is a Gram-positive spore-forming anaerobic bacterium that is the leading cause of nosocomial diarrhea in the developed world. The pathogenesis of C. difficile infections (CDI) is driven by toxin A (TcdA) and toxin B (TcdB), secreted factors that trigger the release of inflammatory mediators and contribute to disruption of the intestinal epithelial barrier. Neutrophils play a key role in the inflammatory response and the induction of pseudomembranous colitis in CDI. TcdA and TcdB alter cytoskeletal signaling and trigger the release of CXCL8/IL-8, a potent neutrophil chemoattractant, from intestinal epithelial cells; however, little is known about the surface receptor(s) that mediate these events. In the current study, we sought to assess whether toxin-induced CXCL8/IL-8 release and barrier dysfunction are driven by the activation of the P2Y6 receptor following the release of UDP, a danger signal, from intoxicated Caco-2 cells. Caco-2 cells express a functional P2Y6 receptor and release measurable amounts of UDP upon exposure to TcdA/B. Toxin-induced CXCL8/IL-8 production and release were attenuated in the presence of a selective P2Y6 inhibitor (MRS2578). This was associated with inhibition of TcdA/B-induced activation of NFκB. Blockade of the P2Y6 receptor also attenuated toxin-induced barrier dysfunction in polarized Caco-2 cells. Lastly, pretreating mice with the P2Y6 receptor antagonists (MSR2578) attenuated TcdA/B-induced inflammation and intestinal permeability in an intrarectal toxin exposure model. Taken together these data outline a novel role for the P2Y6 receptor in the induction of CXCL8/IL-8 production and barrier dysfunction in response to C. difficile toxin exposure and may provide a new therapeutic target for the treatment of CDI."xsd:string |
| http://purl.uniprot.org/citations/24278446 | http://purl.org/dc/terms/identifier | "doi:10.1371/journal.pone.0081491"xsd:string |
| http://purl.uniprot.org/citations/24278446 | http://purl.uniprot.org/core/author | "Altier C."xsd:string |
| http://purl.uniprot.org/citations/24278446 | http://purl.uniprot.org/core/author | "Hansen A."xsd:string |
| http://purl.uniprot.org/citations/24278446 | http://purl.uniprot.org/core/author | "MacDonald J.A."xsd:string |
| http://purl.uniprot.org/citations/24278446 | http://purl.uniprot.org/core/author | "Alston L."xsd:string |
| http://purl.uniprot.org/citations/24278446 | http://purl.uniprot.org/core/author | "Beck P.L."xsd:string |
| http://purl.uniprot.org/citations/24278446 | http://purl.uniprot.org/core/author | "Gendron F.P."xsd:string |
| http://purl.uniprot.org/citations/24278446 | http://purl.uniprot.org/core/author | "Hirota S.A."xsd:string |
| http://purl.uniprot.org/citations/24278446 | http://purl.uniprot.org/core/author | "Tulk S.E."xsd:string |
| http://purl.uniprot.org/citations/24278446 | http://purl.uniprot.org/core/author | "Grassie M.E."xsd:string |
| http://purl.uniprot.org/citations/24278446 | http://purl.uniprot.org/core/author | "Al-Bashir S."xsd:string |
| http://purl.uniprot.org/citations/24278446 | http://purl.uniprot.org/core/author | "Alhassan B.F."xsd:string |
| http://purl.uniprot.org/citations/24278446 | http://purl.uniprot.org/core/author | "Schenck L.P."xsd:string |
| http://purl.uniprot.org/citations/24278446 | http://purl.uniprot.org/core/author | "Veermalla A.T."xsd:string |
| http://purl.uniprot.org/citations/24278446 | http://purl.uniprot.org/core/date | "2013"xsd:gYear |
| http://purl.uniprot.org/citations/24278446 | http://purl.uniprot.org/core/name | "PLoS One"xsd:string |
| http://purl.uniprot.org/citations/24278446 | http://purl.uniprot.org/core/pages | "e81491"xsd:string |
| http://purl.uniprot.org/citations/24278446 | http://purl.uniprot.org/core/title | "The P2Y6 receptor mediates Clostridium difficile toxin-induced CXCL8/IL-8 production and intestinal epithelial barrier dysfunction."xsd:string |
| http://purl.uniprot.org/citations/24278446 | http://purl.uniprot.org/core/volume | "8"xsd:string |
| http://purl.uniprot.org/citations/24278446 | http://www.w3.org/2004/02/skos/core#exactMatch | http://purl.uniprot.org/pubmed/24278446 |
| http://purl.uniprot.org/citations/24278446 | http://xmlns.com/foaf/0.1/primaryTopicOf | https://pubmed.ncbi.nlm.nih.gov/24278446 |
| http://purl.uniprot.org/uniprot/#_Q3UQ86-mappedCitation-24278446 | http://www.w3.org/1999/02/22-rdf-syntax-ns#object | http://purl.uniprot.org/citations/24278446 |
| http://purl.uniprot.org/uniprot/#_Q9ERK9-mappedCitation-24278446 | http://www.w3.org/1999/02/22-rdf-syntax-ns#object | http://purl.uniprot.org/citations/24278446 |