<> <http://www.w3.org/2000/01/rdf-schema#comment> "The repository administrator has not yet configured an RDF license."^^<http://www.w3.org/2001/XMLSchema#string> . <> <http://xmlns.com/foaf/0.1/primaryTopic> <https://discovery.ucl.ac.uk/id/eprint/18990> . <https://discovery.ucl.ac.uk/id/eprint/18990> <http://www.w3.org/1999/02/22-rdf-syntax-ns#type> <http://purl.org/ontology/bibo/Thesis> . <https://discovery.ucl.ac.uk/id/eprint/18990> <http://www.w3.org/1999/02/22-rdf-syntax-ns#type> <http://purl.org/ontology/bibo/Article> . <https://discovery.ucl.ac.uk/id/eprint/18990> <http://purl.org/dc/terms/title> "The role of the NOD2 gene in the pathogenesis of Crohn’s disease"^^<http://www.w3.org/2001/XMLSchema#string> . <https://discovery.ucl.ac.uk/id/eprint/18990> <http://purl.org/ontology/bibo/abstract> "Introduction: Crohn’s disease is characterised by an abnormal inflammatory response\r\npossibly induced by components of enteric bacteria, in genetically susceptible individuals.\r\nMutations in the NOD2 gene are strongly associated with Crohn's disease, although the\r\nmechanisms by which these mutations cause Crohn’s disease remain unknown. Peripheral\r\nblood monocytes (PBMC), a key component of the innate immune system, highly express\r\nNOD2, as do intestinal epithelial Paneth cells. The ligand for NOD2 is Muramyl dipeptide\r\n(MDP), a component of bacterial peptidoglycan. MDP has been shown to be a powerful\r\npriming agent for subsequent stimulation by lipopolysaccharide (LPS) in cell lines and this\r\neffect has been linked to NOD2. Studies of primary mononuclear cells in Crohn’s disease\r\ncomparing the functional effects of the NOD2 mutations had not previously been reported.\r\nAims: To determine the effect of inherited mutations in the NOD2 gene on the cellular\r\nresponses of freshly extracted PBMC to MDP and other bacterial ligands including\r\nmycobacteria. To examine the effect of MDP pre treatment ‘priming’ on PBMC responses\r\nto subsequent LPS stimulation in both normal and Crohn’s disease affected patients\r\nexpressing wild type and mutant NOD2 proteins.\r\nMethods: PBMC from healthy controls (n=12), and Crohn’s disease affected patients who\r\nwere genotypically either wild type (n=12), heterozygous (n=11) or homozygous (n=5) for\r\nthe common disease-causing NOD2 mutations. PBMC were stimulated with bacterial\r\nproducts in vitro, with or without prior stimulation or ‘priming’ with MDP. The\r\ntranscription of selected cytokine genes was determined by real time quantitative RT-PCR\r\nResults: MDP is a weak stimulant of inflammatory responses in PBMC whereas LPS\r\nevoked much stronger responses. Responses to MDP were particularly reduced in PBMC\r\nhomozygous for the NOD2 mutations. Priming with MDP reduced the inflammatory\r\nresponse of normal PBMC to subsequent LPS stimulation. In PBMC carrying two mutant\r\nNOD2 alleles this modulatory effect was reversed and MDP priming caused the\r\ninflammatory response to be enhanced.\r\nConclusion: MDP priming significantly modulates responses of monocytes to LPS. This\r\neffect is altered in patients with Crohn’s disease – possibly related to mutations in the\r\nNOD2 gene. This modulatory effect may explain in part the pro-inflammatory consequence\r\nof mutations in the NOD2 gene and could provide mechanistic understanding of how\r\nmutations in the NOD2 gene may cause Crohn’s disease."^^<http://www.w3.org/2001/XMLSchema#string> . <https://discovery.ucl.ac.uk/id/eprint/18990> <http://purl.org/dc/terms/date> "2009-12" . <https://discovery.ucl.ac.uk/id/document/6241> <http://www.w3.org/1999/02/22-rdf-syntax-ns#type> <http://purl.org/ontology/bibo/Document> . <https://discovery.ucl.ac.uk/id/org/ext-a64c3df5861c6582807add1abaadf2af> <http://www.w3.org/1999/02/22-rdf-syntax-ns#type> <http://xmlns.com/foaf/0.1/Organization> . <https://discovery.ucl.ac.uk/id/org/ext-a64c3df5861c6582807add1abaadf2af> <http://xmlns.com/foaf/0.1/name> "UCL (University College London)"^^<http://www.w3.org/2001/XMLSchema#string> . <https://discovery.ucl.ac.uk/id/eprint/18990> <http://purl.org/dc/terms/issuer> <https://discovery.ucl.ac.uk/id/org/ext-a64c3df5861c6582807add1abaadf2af> . <https://discovery.ucl.ac.uk/id/org/ext-21d723fd0e44b74d73af8792d36d344a> <http://www.w3.org/1999/02/22-rdf-syntax-ns#type> <http://xmlns.com/foaf/0.1/Organization> . <https://discovery.ucl.ac.uk/id/org/ext-21d723fd0e44b74d73af8792d36d344a> <http://xmlns.com/foaf/0.1/name> "Department of Medicine, UCL (University College London)"^^<http://www.w3.org/2001/XMLSchema#string> . <https://discovery.ucl.ac.uk/id/org/ext-21d723fd0e44b74d73af8792d36d344a> <http://purl.org/dc/terms/isPartOf> <https://discovery.ucl.ac.uk/id/org/ext-a64c3df5861c6582807add1abaadf2af> . <https://discovery.ucl.ac.uk/id/eprint/18990> <http://purl.org/dc/terms/issuer> <https://discovery.ucl.ac.uk/id/org/ext-21d723fd0e44b74d73af8792d36d344a> . <https://discovery.ucl.ac.uk/id/org/ext-a64c3df5861c6582807add1abaadf2af> <http://purl.org/dc/terms/hasPart> <https://discovery.ucl.ac.uk/id/org/ext-21d723fd0e44b74d73af8792d36d344a> . <https://discovery.ucl.ac.uk/id/eprint/18990> <http://purl.org/ontology/bibo/status> <http://purl.org/ontology/bibo/status/unpublished> . <https://discovery.ucl.ac.uk/id/eprint/18990> <http://purl.org/dc/terms/creator> <https://discovery.ucl.ac.uk/id/person/ext-8f61b71a1cc7c40ff794bb5877c05a54> . <https://discovery.ucl.ac.uk/id/eprint/18990> <http://purl.org/ontology/bibo/authorList> <https://discovery.ucl.ac.uk/id/eprint/18990#authors> . <https://discovery.ucl.ac.uk/id/eprint/18990#authors> <http://www.w3.org/1999/02/22-rdf-syntax-ns#_1> <https://discovery.ucl.ac.uk/id/person/ext-8f61b71a1cc7c40ff794bb5877c05a54> . <https://discovery.ucl.ac.uk/id/person/ext-8f61b71a1cc7c40ff794bb5877c05a54> <http://www.w3.org/1999/02/22-rdf-syntax-ns#type> <http://xmlns.com/foaf/0.1/Person> . <https://discovery.ucl.ac.uk/id/person/ext-8f61b71a1cc7c40ff794bb5877c05a54> <http://xmlns.com/foaf/0.1/givenName> "T.A."^^<http://www.w3.org/2001/XMLSchema#string> . <https://discovery.ucl.ac.uk/id/person/ext-8f61b71a1cc7c40ff794bb5877c05a54> <http://xmlns.com/foaf/0.1/familyName> "Chalmers-Watson"^^<http://www.w3.org/2001/XMLSchema#string> . <https://discovery.ucl.ac.uk/id/person/ext-8f61b71a1cc7c40ff794bb5877c05a54> <http://xmlns.com/foaf/0.1/name> "T.A. Chalmers-Watson"^^<http://www.w3.org/2001/XMLSchema#string> . <https://discovery.ucl.ac.uk/id/eprint/18990> <http://www.w3.org/1999/02/22-rdf-syntax-ns#type> <http://eprints.org/ontology/EPrint> . <https://discovery.ucl.ac.uk/id/eprint/18990> <http://www.w3.org/1999/02/22-rdf-syntax-ns#type> <http://eprints.org/ontology/ThesisEPrint> . <https://discovery.ucl.ac.uk/id/eprint/18990> <http://purl.org/dc/terms/isPartOf> <https://discovery.ucl.ac.uk/id/repository> . <https://discovery.ucl.ac.uk/id/eprint/18990> <http://eprints.org/ontology/hasDocument> <https://discovery.ucl.ac.uk/id/document/6241> . <https://discovery.ucl.ac.uk/id/document/6241> <http://www.w3.org/1999/02/22-rdf-syntax-ns#type> <http://eprints.org/ontology/Document> . <https://discovery.ucl.ac.uk/id/document/6241> <http://www.w3.org/2000/01/rdf-schema#label> "The role of the NOD2 gene in the pathogenesis of Crohn’s disease (PDF)"^^<http://www.w3.org/2001/XMLSchema#string> . <https://discovery.ucl.ac.uk/id/document/6241> 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<https://discovery.ucl.ac.uk/id/document/81440> <http://www.w3.org/1999/02/22-rdf-syntax-ns#type> <http://eprints.org/ontology/Document> . <https://discovery.ucl.ac.uk/id/document/81440> <http://www.w3.org/2000/01/rdf-schema#label> "The role of the NOD2 gene in the pathogenesis of Crohn’s disease (Image (PNG))"^^<http://www.w3.org/2001/XMLSchema#string> . <https://discovery.ucl.ac.uk/id/document/81440> <http://eprints.org/relation/isVolatileVersionOf> <https://discovery.ucl.ac.uk/id/document/6241> . <https://discovery.ucl.ac.uk/id/document/81440> <http://eprints.org/relation/ispreviewThumbnailVersionOf> <https://discovery.ucl.ac.uk/id/document/6241> . <https://discovery.ucl.ac.uk/id/document/81440> <http://eprints.org/relation/isVersionOf> <https://discovery.ucl.ac.uk/id/document/6241> . <https://discovery.ucl.ac.uk/id/document/81440> <http://eprints.org/ontology/hasFile> <https://discovery.ucl.ac.uk/id/eprint/18990/2/preview.png> . <https://discovery.ucl.ac.uk/id/document/81440> <http://purl.org/dc/terms/hasPart> <https://discovery.ucl.ac.uk/id/eprint/18990/2/preview.png> . <https://discovery.ucl.ac.uk/id/eprint/18990/2/preview.png> <http://www.w3.org/2000/01/rdf-schema#label> "preview.png"^^<http://www.w3.org/2001/XMLSchema#string> . <https://discovery.ucl.ac.uk/id/eprint/18990> <http://eprints.org/ontology/hasDocument> <https://discovery.ucl.ac.uk/id/document/106511> . <https://discovery.ucl.ac.uk/id/document/106511> <http://www.w3.org/1999/02/22-rdf-syntax-ns#type> <http://eprints.org/ontology/Document> . <https://discovery.ucl.ac.uk/id/document/106511> <http://www.w3.org/2000/01/rdf-schema#label> "The role of the NOD2 gene in the pathogenesis of Crohn’s disease (Other)"^^<http://www.w3.org/2001/XMLSchema#string> . <https://discovery.ucl.ac.uk/id/document/106511> <http://eprints.org/relation/isVersionOf> <https://discovery.ucl.ac.uk/id/document/6241> . <https://discovery.ucl.ac.uk/id/document/106511> <http://eprints.org/relation/isVolatileVersionOf> 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<https://discovery.ucl.ac.uk/id/eprint/18990/> <http://purl.org/dc/elements/1.1/format> "text/html" . <https://discovery.ucl.ac.uk/id/eprint/18990/> <http://xmlns.com/foaf/0.1/primaryTopic> <https://discovery.ucl.ac.uk/id/eprint/18990> . <https://discovery.ucl.ac.uk/id/subject/3900> <http://www.w3.org/1999/02/22-rdf-syntax-ns#type> <http://www.w3.org/2004/02/skos/core#Concept> . <https://discovery.ucl.ac.uk/id/subject/3900> <http://www.w3.org/2004/02/skos/core#prefLabel> "Department of Medicine"@en . <https://discovery.ucl.ac.uk/id/eprint/18990> <http://purl.org/dc/terms/subject> <https://discovery.ucl.ac.uk/id/subject/3900> .