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Cited by 377

The DOI matches its Crossref record; 38 of the 38 references it cites were found in a registry or an index.

RNA released from necrotic synovial fluid cells activates rheumatoid arthritis synovial fibroblasts via toll‐like receptor 3

Brentano, Fabia, Schorr, Olivier, Gay, Renate E., Gay, Steffen, Kyburz, Diego·2005·Arthritis & Rheumatism

Abstract

Objective: To assess the expression of Toll‐like receptor 3 (TLR‐3) protein in synovial tissues and cultured synovial fibroblasts obtained from patients with rheumatoid arthritis (RA) and osteoarthritis (OA) and to investigate the consequences of stimulation of cultured synovial fibroblasts with TLR‐3 ligands. Methods: TLR‐3 expression in synovial tissues was determined by immunohistochemistry and immunofluorescence, and expression in cultured RA synovial fibroblasts (RASFs) was determined by fluorescence‐activated cell sorting and real‐time polymerase chain reaction techniques. TLR‐3 signaling was assessed by incubating RASFs with poly(I‐C), lipopolysaccharide, palmitoyl‐3‐cysteine‐serine‐lysine‐4, or necrotic synovial fluid cells from RA patients in the presence or absence of hydroxychloroquine or Benzonase. Subsequent determination of interferon‐β (IFNβ), CXCL10, CCL5, and interleukin‐6 (IL‐6) protein production in the culture supernatants was performed by enzyme‐linked immunosorbent assays. Results: TLR‐3 protein expression was found to be higher in RA synovial tissues than in OA synovial tissues. TLR‐3 expression was localized predominantly in the synovial lining, with a majority of the TLR‐3–expressing cells coexpressing fibroblast markers. Stimulation of cultured RASFs with the TLR‐3 ligand poly(I‐C) resulted in the production of high levels of IFNβ, CXCL10, CCL5, and IL‐6 protein. Similarly, coincubation of RASFs with necrotic synovial fluid cells from patients with RA resulted in up‐regulation of these cytokines and chemokines in a TLR‐3–dependent manner. Conclusion: Our findings demonstrate the expression of TLR‐3 in RA synovial tissue and the activation of RASFs in vitro by the TLR‐3 ligand poly(I‐C) as well as by necrotic RA synovial fluid cells, and indicate that RNA released from necrotic cells might act as an endogenous TLR‐3 ligand for the stimulation of proinflammatory gene expression in RASFs.

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Metadata

Authors
Brentano, F., Schorr, O., Gay, R. E., Gay, S., & Kyburz, D.
Venue
Arthritis & Rheumatism
Publisher
Wiley
Published
2005-09
Volume
52
Issue
9
Pages
2656-2665
ISSN
  • 0004-3591 (ISSN-L)
  • 1529-0131
OpenAlex
W1974545869
Cited by
377
References
38
FWCI
11.27
Type
journal article
Language
en
Open access
closed

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CoChat. (2026). Citation check: RNA released from necrotic synovial fluid cells activates rheumatoid arthritis synovial fibroblasts via toll‐like receptor 3. https://app.cochat.ai/papers/10.1002/art.21273
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Brentano, F., Schorr, O., Gay, R. E., Gay, S., & Kyburz, D. (2005). RNA released from necrotic synovial fluid cells activates rheumatoid arthritis synovial fibroblasts via toll‐like receptor 3. Arthritis & Rheumatism. https://doi.org/10.1002/art.21273

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