| http://purl.uniprot.org/citations/30990796 | http://www.w3.org/1999/02/22-rdf-syntax-ns#type | http://purl.uniprot.org/core/Journal_Citation |
| http://purl.uniprot.org/citations/30990796 | http://www.w3.org/2000/01/rdf-schema#comment | "The polarization of macrophages is regulated by transcription factors such as nuclear factor kappa B (NF-κB) and activator protein 1 (AP-1). In this manuscript, we delineated the role of the transcription factor Fos-related antigen 1 (Fra-1) during macrophage activation and development of arthritis. Network level interaction analysis of microarray data derived from Fra-1- or Fra-2-deficient macrophages revealed a central role of Fra-1, but not of Fra-2 in orchestrating the expression of genes related to wound response, toll-like receptor activation and interleukin signaling. Chromatin-immunoprecipitation (ChIP)-sequencing and standard ChIP analyses of macrophages identified arginase 1 (Arg1) as a target of Fra-1. Luciferase reporter assays revealed that Fra-1 down-regulated Arg1 expression by direct binding to the promoter region. Using macrophage-specific Fra-1- or Fra-2-deficient mice, we observed an enhanced expression and activity of Arg1 and a reduction of arthritis in the absence of Fra-1, but not of Fra-2. This phenotype was reversed by treatment with the arginase inhibitor Nω-hydroxy-nor-L-arginine, while ʟ-arginine supplementation increased arginase activity and alleviated arthritis, supporting the notion that reduced arthritis in macrophage-specific Fra-1-deficient mice resulted from enhanced Arg1 expression and activity. Moreover, patients with active RA showed increased Fra-1 expression in the peripheral blood and elevated Fra-1 protein in synovial macrophages compared to RA patients in remission. In addition, the Fra-1/ARG1 ratio in synovial macrophages was related to RA disease activity. In conclusion, these data suggest that Fra-1 orchestrates the inflammatory state of macrophages by inhibition of Arg1 expression and thereby impedes the resolution of inflammation."xsd:string |
| http://purl.uniprot.org/citations/30990796 | http://purl.org/dc/terms/identifier | "doi:10.1172/jci96832"xsd:string |
| http://purl.uniprot.org/citations/30990796 | http://purl.uniprot.org/core/author | "Chen X."xsd:string |
| http://purl.uniprot.org/citations/30990796 | http://purl.uniprot.org/core/author | "Cao S."xsd:string |
| http://purl.uniprot.org/citations/30990796 | http://purl.uniprot.org/core/author | "Bogdan C."xsd:string |
| http://purl.uniprot.org/citations/30990796 | http://purl.uniprot.org/core/author | "Schleicher U."xsd:string |
| http://purl.uniprot.org/citations/30990796 | http://purl.uniprot.org/core/author | "Rech J."xsd:string |
| http://purl.uniprot.org/citations/30990796 | http://purl.uniprot.org/core/author | "Jordan J."xsd:string |
| http://purl.uniprot.org/citations/30990796 | http://purl.uniprot.org/core/author | "Ekici A."xsd:string |
| http://purl.uniprot.org/citations/30990796 | http://purl.uniprot.org/core/author | "Uebe S."xsd:string |
| http://purl.uniprot.org/citations/30990796 | http://purl.uniprot.org/core/author | "Vera J."xsd:string |
| http://purl.uniprot.org/citations/30990796 | http://purl.uniprot.org/core/author | "Bozec A."xsd:string |
| http://purl.uniprot.org/citations/30990796 | http://purl.uniprot.org/core/author | "Schett G."xsd:string |
| http://purl.uniprot.org/citations/30990796 | http://purl.uniprot.org/core/author | "Eberhardt M."xsd:string |
| http://purl.uniprot.org/citations/30990796 | http://purl.uniprot.org/core/author | "Schnelzer A."xsd:string |
| http://purl.uniprot.org/citations/30990796 | http://purl.uniprot.org/core/author | "Canete J.D."xsd:string |
| http://purl.uniprot.org/citations/30990796 | http://purl.uniprot.org/core/author | "Eriksson D."xsd:string |
| http://purl.uniprot.org/citations/30990796 | http://purl.uniprot.org/core/author | "Bauerle T."xsd:string |
| http://purl.uniprot.org/citations/30990796 | http://purl.uniprot.org/core/author | "Ramming A."xsd:string |
| http://purl.uniprot.org/citations/30990796 | http://purl.uniprot.org/core/author | "Hannemann N."xsd:string |
| http://purl.uniprot.org/citations/30990796 | http://purl.uniprot.org/core/date | "2019"xsd:gYear |
| http://purl.uniprot.org/citations/30990796 | http://purl.uniprot.org/core/name | "J Clin Invest"xsd:string |
| http://purl.uniprot.org/citations/30990796 | http://purl.uniprot.org/core/pages | "2669-2684"xsd:string |
| http://purl.uniprot.org/citations/30990796 | http://purl.uniprot.org/core/title | "Transcription factor Fra-1 targets arginase-1 to enhance macrophage-mediated inflammation in arthritis."xsd:string |