RNA released from necrotic synovial fluid cells activates rheumatoid arthritis synovial fibroblasts via Toll-like receptor 3 - PubMed (original) (raw)
. 2005 Sep;52(9):2656-65.
doi: 10.1002/art.21273.
Affiliations
- PMID: 16142732
- DOI: 10.1002/art.21273
Free article
RNA released from necrotic synovial fluid cells activates rheumatoid arthritis synovial fibroblasts via Toll-like receptor 3
Fabia Brentano et al. Arthritis Rheum. 2005 Sep.
Free article
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-beta (IFNbeta), 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 IFNbeta, 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.
Similar articles
- Bacterial peptidoglycans but not CpG oligodeoxynucleotides activate synovial fibroblasts by toll-like receptor signaling.
Kyburz D, Rethage J, Seibl R, Lauener R, Gay RE, Carson DA, Gay S. Kyburz D, et al. Arthritis Rheum. 2003 Mar;48(3):642-50. doi: 10.1002/art.10848. Arthritis Rheum. 2003. PMID: 12632416 - Overexpression of toll-like receptors 3 and 4 in synovial tissue from patients with early rheumatoid arthritis: toll-like receptor expression in early and longstanding arthritis.
Ospelt C, Brentano F, Rengel Y, Stanczyk J, Kolling C, Tak PP, Gay RE, Gay S, Kyburz D. Ospelt C, et al. Arthritis Rheum. 2008 Dec;58(12):3684-92. doi: 10.1002/art.24140. Arthritis Rheum. 2008. PMID: 19035519 - Expression of toll-like receptors 2 and 4 in rheumatoid synovial tissue and regulation by proinflammatory cytokines interleukin-12 and interleukin-18 via interferon-gamma.
Radstake TR, Roelofs MF, Jenniskens YM, Oppers-Walgreen B, van Riel PL, Barrera P, Joosten LA, van den Berg WB. Radstake TR, et al. Arthritis Rheum. 2004 Dec;50(12):3856-65. doi: 10.1002/art.20678. Arthritis Rheum. 2004. PMID: 15593217 - Rheumatoid arthritis progression mediated by activated synovial fibroblasts.
Neumann E, Lefèvre S, Zimmermann B, Gay S, Müller-Ladner U. Neumann E, et al. Trends Mol Med. 2010 Oct;16(10):458-68. doi: 10.1016/j.molmed.2010.07.004. Epub 2010 Aug 24. Trends Mol Med. 2010. PMID: 20739221 Review. - The role of Toll-like receptor signalling in the pathogenesis of arthritis.
Brentano F, Kyburz D, Schorr O, Gay R, Gay S. Brentano F, et al. Cell Immunol. 2005 Feb;233(2):90-6. doi: 10.1016/j.cellimm.2005.04.018. Cell Immunol. 2005. PMID: 15963480 Review.
Cited by
- DAMPs and radiation injury.
Yamaga S, Aziz M, Murao A, Brenner M, Wang P. Yamaga S, et al. Front Immunol. 2024 Jan 25;15:1353990. doi: 10.3389/fimmu.2024.1353990. eCollection 2024. Front Immunol. 2024. PMID: 38333215 Free PMC article. Review. - Network-Based In Silico Analysis of New Combinations of Modern Drug Targets with Methotrexate for Response-Based Treatment of Rheumatoid Arthritis.
Assefi M, Lewandrowski KU, Lorio M, Fiorelli RKA; Brazilian Society For Thoracic Surgery—Sociedade Brasileira de Cirurgia Torácica (SBCT); Landgraeber S, Sharafshah A. Assefi M, et al. J Pers Med. 2023 Oct 29;13(11):1550. doi: 10.3390/jpm13111550. J Pers Med. 2023. PMID: 38003865 Free PMC article. Review. - Unrevealing the Role of TLRs in the Pathogenesis of Autoimmune Disease by Using Mouse Model of Diabetes.
Panfili E, Orecchini E, Mondanelli G. Panfili E, et al. Methods Mol Biol. 2023;2700:187-198. doi: 10.1007/978-1-0716-3366-3_11. Methods Mol Biol. 2023. PMID: 37603182 - Global trends in research of fibroblasts associated with rheumatoid diseases in the 21st century: A bibliometric analysis.
Huang R, Jin M, Liu Y, Lu Y, Zhang M, Yan P, Xian S, Wang S, Zhang H, Zhang X, Chen S, Lu B, Yang Y, Huang Z, Liu X, Ji S. Huang R, et al. Front Immunol. 2023 Feb 10;14:1098977. doi: 10.3389/fimmu.2023.1098977. eCollection 2023. Front Immunol. 2023. PMID: 36845163 Free PMC article. - LL-37-dsRNA Complexes Modulate Immune Response via RIG-I in Oral Keratinocytes.
Kato H, Ohta K, Akagi M, Fukada S, Sakuma M, Naruse T, Nishi H, Shigeishi H, Takechi M, Aikawa T. Kato H, et al. Inflammation. 2023 Jun;46(3):808-823. doi: 10.1007/s10753-023-01787-5. Epub 2023 Feb 10. Inflammation. 2023. PMID: 36763254
Publication types
MeSH terms
Substances
LinkOut - more resources
Full Text Sources
Other Literature Sources
Medical