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http://purl.uniprot.org/citations/36672263http://www.w3.org/1999/02/22-rdf-syntax-ns#typehttp://purl.uniprot.org/core/Journal_Citation
http://purl.uniprot.org/citations/36672263http://www.w3.org/2000/01/rdf-schema#comment"Background: Fibroblast-like synoviocytes (FLSs) are essential mediators in the expansive growth and invasiveness of rheumatoid synovitis, and patients with a fibroblastic-rich pauci-immune pathotype respond poorly to currently approved antirheumatic drugs. Galectin-9 (Gal-9) has been reported to directly modulate rheumatoid arthritis (RA) FLSs and to hold both pro- and anti-inflammatory properties. The objective of this study was to evaluate clinical and pathogenic aspects of Gal-9 in RA, combining national patient cohorts and cellular models. Methods: Soluble Gal-9 was measured in plasma from patients with newly diagnosed, treatment-naïve RA (n = 98). The disease activity score 28-joint count C-reactive protein (DAS28CRP) and total Sharp score were used to evaluate the disease course serially over a two-year period. Plasma and synovial fluid samples were examined for soluble Gal-9 in patients with established RA (n = 18). A protein array was established to identify Gal-9 binding partners in the extracellular matrix (ECM). Synovial fluid mononuclear cells (SFMCs), harvested from RA patients, were used to obtain synovial-fluid derived FLSs (SF-FLSs) (n = 7). FLSs from patients suffering from knee Osteoarthritis (OA) were collected from patients when undergoing joint replacement surgery (n = 5). Monocultures of SF-FLSs (n = 6) and autologous co-cultures of SF-FLSs and peripheral blood mononuclear cells (PBMCs) were cultured with and without a neutralizing anti-Gal-9 antibody (n = 7). The mono- and co-cultures were subsequently analyzed by flow cytometry, MTT assay, and ELISA. Results: Patients with early and established RA had persistently increased plasma levels of Gal-9 compared with healthy controls (HC). The plasma levels of Gal-9 were associated with disease activity and remained unaffected when adding a TNF-inhibitor to their standard treatment. Gal-9 levels were elevated in the synovial fluid of established RA patients with advanced disease, compared with corresponding plasma samples. Gal-9 adhered to fibronectin, laminin and thrombospondin, while not to interstitial collagens in the ECM protein array. In vitro, a neutralizing Gal-9 antibody decreased MCP-1 and IL-6 production from both RA FLSs and OA FLSs. In co-cultures of autologous RA FLSs and PBMCs, the neutralization of Gal-9 also decreased MCP-1 and IL-6 production, without affecting the proportion of inflammatory FLSs. Conclusions: In RA, pretreatment plasma Gal-9 levels in early RA were increased and correlated with clinical disease activity. Gal-9 levels remained increased despite a significant reduction in the disease activity score in patients with early RA. The in vitro neutralization of Gal-9 decreased both MCP-1 and IL-6 production in an inflammatory subset of RA FLSs. Collectively these findings indicate that the persistent overexpression of Gal-9 in RA may modulate synovial FLS activities and could be involved in the maintenance of subclinical disease activity in RA."xsd:string
http://purl.uniprot.org/citations/36672263http://purl.org/dc/terms/identifier"doi:10.3390/cells12020327"xsd:string
http://purl.uniprot.org/citations/36672263http://purl.uniprot.org/core/author"Cummings R.D."xsd:string
http://purl.uniprot.org/citations/36672263http://purl.uniprot.org/core/author"Busson P."xsd:string
http://purl.uniprot.org/citations/36672263http://purl.uniprot.org/core/author"Junker P."xsd:string
http://purl.uniprot.org/citations/36672263http://purl.uniprot.org/core/author"Leffler H."xsd:string
http://purl.uniprot.org/citations/36672263http://purl.uniprot.org/core/author"Deleuran B."xsd:string
http://purl.uniprot.org/citations/36672263http://purl.uniprot.org/core/author"Kragstrup T.W."xsd:string
http://purl.uniprot.org/citations/36672263http://purl.uniprot.org/core/author"Stengaard-Pedersen K."xsd:string
http://purl.uniprot.org/citations/36672263http://purl.uniprot.org/core/author"Nielsen M.A."xsd:string
http://purl.uniprot.org/citations/36672263http://purl.uniprot.org/core/author"Mehta A.Y."xsd:string
http://purl.uniprot.org/citations/36672263http://purl.uniprot.org/core/author"Horslev-Petersen K."xsd:string
http://purl.uniprot.org/citations/36672263http://purl.uniprot.org/core/author"Ostergaard M."xsd:string
http://purl.uniprot.org/citations/36672263http://purl.uniprot.org/core/author"Koster D."xsd:string
http://purl.uniprot.org/citations/36672263http://purl.uniprot.org/core/author"Hetland M.L."xsd:string
http://purl.uniprot.org/citations/36672263http://purl.uniprot.org/core/author"Hvid M."xsd:string
http://purl.uniprot.org/citations/36672263http://purl.uniprot.org/core/date"2023"xsd:gYear
http://purl.uniprot.org/citations/36672263http://purl.uniprot.org/core/name"Cells"xsd:string
http://purl.uniprot.org/citations/36672263http://purl.uniprot.org/core/pages"327"xsd:string
http://purl.uniprot.org/citations/36672263http://purl.uniprot.org/core/title"Increased Galectin-9 Levels Correlate with Disease Activity in Patients with DMARD-Naive Rheumatoid Arthritis and Modulate the Secretion of MCP-1 and IL-6 from Synovial Fibroblasts."xsd:string
http://purl.uniprot.org/citations/36672263http://purl.uniprot.org/core/volume"12"xsd:string
http://purl.uniprot.org/citations/36672263http://www.w3.org/2004/02/skos/core#exactMatchhttp://purl.uniprot.org/pubmed/36672263
http://purl.uniprot.org/citations/36672263http://xmlns.com/foaf/0.1/primaryTopicOfhttps://pubmed.ncbi.nlm.nih.gov/36672263
http://purl.uniprot.org/uniprot/#_A0A1C9J7U0-mappedCitation-36672263http://www.w3.org/1999/02/22-rdf-syntax-ns#objecthttp://purl.uniprot.org/citations/36672263
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