| http://purl.uniprot.org/citations/11435459 | http://www.w3.org/1999/02/22-rdf-syntax-ns#type | http://purl.uniprot.org/core/Journal_Citation |
| http://purl.uniprot.org/citations/11435459 | http://www.w3.org/2000/01/rdf-schema#comment | "Mitogen-activated protein kinase (MAPK) cascades are involved in inflammation and tissue destruction in rheumatoid arthritis (RA). In particular, c-Jun N-terminal kinase (JNK) is highly activated in RA fibroblast-like synoviocytes and synovium. However, defining the precise function of this kinase has been difficult because a selective JNK inhibitor has not been available. We now report the use of a novel selective JNK inhibitor and JNK knockout mice to determine the function of JNK in synoviocyte biology and inflammatory arthritis. The novel JNK inhibitor SP600125 (anthra[1,9-cd]pyrazol-6(2H)-one) completely blocked IL-1--induced accumulation of phospho-Jun and induction of c-Jun transcription in synoviocytes. Furthermore, AP-1 binding and collagenase mRNA accumulation were completely suppressed by SP600125. In contrast, complete inhibition of p38 had no effect, and ERK inhibition had only a modest effect. The essential role of JNK was confirmed in cultured synoviocytes from JNK1 knockout mice and JNK2 knockout mice, each of which had a partial defect in IL-1--induced AP-1 activation and collagenase-3 expression. Administration of SP600125 modestly decreased the rat paw swelling in rat adjuvant-induced arthritis. More striking was the near-complete inhibition of radiographic damage that was associated with decreased AP-1 activity and collagenase-3 gene expression. Therefore, JNK is a critical MAPK pathway for IL-1--induced collagenase gene expression in synoviocytes and in joint arthritis, indicating that JNK is an important therapeutic target for RA."xsd:string |
| http://purl.uniprot.org/citations/11435459 | http://purl.org/dc/terms/identifier | "doi:10.1172/jci12466"xsd:string |
| http://purl.uniprot.org/citations/11435459 | http://purl.uniprot.org/core/author | "Bennett B."xsd:string |
| http://purl.uniprot.org/citations/11435459 | http://purl.uniprot.org/core/author | "Chang L."xsd:string |
| http://purl.uniprot.org/citations/11435459 | http://purl.uniprot.org/core/author | "Yang L."xsd:string |
| http://purl.uniprot.org/citations/11435459 | http://purl.uniprot.org/core/author | "Boyle D.L."xsd:string |
| http://purl.uniprot.org/citations/11435459 | http://purl.uniprot.org/core/author | "Firestein G.S."xsd:string |
| http://purl.uniprot.org/citations/11435459 | http://purl.uniprot.org/core/author | "Han Z."xsd:string |
| http://purl.uniprot.org/citations/11435459 | http://purl.uniprot.org/core/author | "Karin M."xsd:string |
| http://purl.uniprot.org/citations/11435459 | http://purl.uniprot.org/core/author | "Manning A.M."xsd:string |
| http://purl.uniprot.org/citations/11435459 | http://purl.uniprot.org/core/date | "2001"xsd:gYear |
| http://purl.uniprot.org/citations/11435459 | http://purl.uniprot.org/core/name | "J Clin Invest"xsd:string |
| http://purl.uniprot.org/citations/11435459 | http://purl.uniprot.org/core/pages | "73-81"xsd:string |
| http://purl.uniprot.org/citations/11435459 | http://purl.uniprot.org/core/title | "c-Jun N-terminal kinase is required for metalloproteinase expression and joint destruction in inflammatory arthritis."xsd:string |
| http://purl.uniprot.org/citations/11435459 | http://purl.uniprot.org/core/volume | "108"xsd:string |
| http://purl.uniprot.org/citations/11435459 | http://www.w3.org/2004/02/skos/core#exactMatch | http://purl.uniprot.org/pubmed/11435459 |
| http://purl.uniprot.org/citations/11435459 | http://xmlns.com/foaf/0.1/primaryTopicOf | https://pubmed.ncbi.nlm.nih.gov/11435459 |
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| http://purl.uniprot.org/uniprot/#_A0A2I3BPL3-mappedCitation-11435459 | http://www.w3.org/1999/02/22-rdf-syntax-ns#object | http://purl.uniprot.org/citations/11435459 |
| http://purl.uniprot.org/uniprot/#_A3KBF5-mappedCitation-11435459 | http://www.w3.org/1999/02/22-rdf-syntax-ns#object | http://purl.uniprot.org/citations/11435459 |
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