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Increased Galectin-...
Increased Galectin-9 Levels Correlate with Disease Activity in Patients with DMARD-Naïve Rheumatoid Arthritis and Modulate the Secretion of MCP-1 and IL-6 from Synovial Fibroblasts
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- Nielsen, Morten A. (författare)
- Aarhus University Hospital,Aarhus University
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- Køster, Ditte (författare)
- Aarhus University
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- Mehta, Akul Y. (författare)
- Harvard Medical School
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- Stengaard-Pedersen, Kristian (författare)
- Aarhus University Hospital
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- Busson, Pierre (författare)
- University of Paris-Saclay
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- Junker, Peter (författare)
- Odense University Hospital
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- Hørslev-Petersen, Kim (författare)
- University of Southern Denmark
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- Hetland, Merete Lund (författare)
- Copenhagen University Hospital,University of Copenhagen
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- Østergaard, Mikkel (författare)
- Copenhagen University Hospital,University of Copenhagen
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- Hvid, Malene (författare)
- Aarhus University
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- Leffler, Hakon (författare)
- Lund University,Lunds universitet,Avdelningen för mikrobiologi, immunologi och glykobiologi - MIG,Institutionen för laboratoriemedicin,Medicinska fakulteten,Division of Microbiology, Immunology and Glycobiology - MIG,Department of Laboratory Medicine,Faculty of Medicine
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- Kragstrup, Tue W. (författare)
- Aarhus University Hospital,Aarhus University
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- Cummings, Richard D. (författare)
- Harvard Medical School
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- Deleuran, Bent (författare)
- Aarhus University,Aarhus University Hospital
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(creator_code:org_t)
- 2023-01-15
- 2023
- Engelska.
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Ingår i: Cells. - : MDPI AG. - 2073-4409. ; 12:2
- Relaterad länk:
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http://dx.doi.org/10... (free)
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https://lup.lub.lu.s...
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https://doi.org/10.3...
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Abstract
Ämnesord
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- 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.
Ämnesord
- MEDICIN OCH HÄLSOVETENSKAP -- Klinisk medicin -- Reumatologi och inflammation (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Clinical Medicine -- Rheumatology and Autoimmunity (hsv//eng)
Nyckelord
- fibroblast
- Galectin-9
- inflammation
- rheumatoid arthritis
Publikations- och innehållstyp
- art (ämneskategori)
- ref (ämneskategori)
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Cells
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- Av författaren/redakt...
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Nielsen, Morten ...
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Køster, Ditte
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Mehta, Akul Y.
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Stengaard-Peders ...
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Busson, Pierre
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Junker, Peter
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visa fler...
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Hørslev-Petersen ...
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Hetland, Merete ...
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Østergaard, Mikk ...
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Hvid, Malene
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Leffler, Hakon
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Kragstrup, Tue W ...
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Cummings, Richar ...
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Deleuran, Bent
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