Antigen-presenting cells containing bacterial peptidoglycan in synovial tissues of rheumatoid arthritis patients coexpress costimulatory molecules and cytokines

Schrijver, Ingrid A.; Melief, Marie-José; Tak, Paul P.; Hazenberg, M. P.; Laman, JD

doi:10.1002/1529-0131(200010)43:10<2160::aid-anr3>3.0.co;2-t

Cited by 90 publications

(60 citation statements)

References 67 publications

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“…In support of this, LPS has been detected in periprosthetic tissue from patients with inflammatory arthritis and aseptic loosening [73]. Moreover, peptidoglycan, a PAMP produced by both Gram-negative and Gram-positive bacteria, exists in synovial tissue from patients with osteoarthritis and rheumatoid arthritis [16,96] and, therefore, likely exists in periprosthetic tissue of patients with aseptic loosening. One potential source of PAMPs during aseptic loosening is the bacteria present in the biofilms found on many loose implants despite the absence of clinical signs of infection [21,47,54,74,76,107,109].…”

Section: Toll-like Receptorsmentioning

confidence: 79%

Do Genetic Susceptibility, Toll-like Receptors, and Pathogen-associated Molecular Patterns Modulate the Effects of Wear?

Greenfield

2014

Clin Orthop Relat Res

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Background Overwhelming evidence supports the concept that wear particles are the primary initiator of aseptic loosening of orthopaedic implants. It is likely, however, that other factors modulate the biologic response to wear particles. This review focuses on three potential other factors: genetic susceptibility, Toll-like receptors (TLRs), and bacterial pathogen-associated molecular patterns (PAMPs). Where Are We Now? Considerable evidence is emerging that both genetic susceptibility and TLR activation are important factors that modulate the biologic response to wear particles, but it remains controversial whether bacterial PAMPs also do so. Where Do We Need to Go? Detailed understanding of the roles of these other factors may lead to identification of novel therapeutic targets for patients with aseptic loosening. How Do We Get There? Highest priority should be given to polymorphism replication studies with large numbers of patients and studies to replicate the reported correlation between bacterial biofilms and the severity of aseptic loosening.

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Section: Toll-like Receptorsmentioning

confidence: 79%

Do Genetic Susceptibility, Toll-like Receptors, and Pathogen-associated Molecular Patterns Modulate the Effects of Wear?

Greenfield

2014

Clin Orthop Relat Res

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“…161 In addition, bacterial peptideglycans was demonstrated in the synovial macrophages. 162 Exogenous PAMPs can evoke initial immune response via TLRs, which has been implicated to be involved in triggering of joint inflammation and disease flares in RA.…”

Section: Pamps and Damps In Ra Synovial Tissuesmentioning

confidence: 99%

Toll-like Receptor

Takagi

2011

J Clin Exp Hematopathol

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Toll like receptor (TLR), one of the key functions of innate immune system, can recognize not only exogenous pathogenassociated molecular patterns, namely PAMPs, but also endogenous molecules created upon tissue injury, sterile inflammation and degeneration. Endogenous TLR ligands are called as damage-associated molecular patters (DAMPs), including endogenous molecules released by activated and necrotic cells, and extracellular matrix molecules. DAMPs are also known as alarmins. TLR research has brought about new insights in the rheumatic diseases. Previous reports suggest that TLRs and the signal pathways intensively contribute to the pathogenesis of rheumatoid arthritis (RA) and other arthritic conditions with interaction of various TLR ligands. Accumulated knowledge of TLR system is summarized to overlook TLRs and the signaling pathway in arthritis conditions, with special reference to RA. 〔J Clin Exp Hematopathol 51(2) : 77-92, 2011〕

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“…Indeed, TLR ligands of exogenous origin such as bacterial peptidoglycans and CpG-containing DNA, activating TLR-2 and TLR-9, respectively, have been found in the synovial fluid of patients with RA (5,6). In experimental models of arthritis, TLR ligands have repeatedly been used to induce the disease in susceptible animals; for instance, intraarticular injection of streptococcal cell wall fragments, double-stranded RNA, or CpGcontaining DNA, which mainly signal through TLR-2, TLR-3, and TLR-9, respectively, can induce arthritis (7)(8)(9).…”

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confidence: 99%

Inhibition of toll‐like receptor 4 breaks the inflammatory loop in autoimmune destructive arthritis

Abdollahi‐Roodsaz

Joosten

Roelofs

et al. 2007

Arthritis & Rheumatism

283

219

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Objective. Degeneration of extracellular matrix of cartilage leads to the production of molecules capable of activating the immune system via Toll-like receptor 4 (TLR-4). The objective of this study was to investigate the involvement of TLR-4 activation in the development and progression of autoimmune destructive arthritis.Methods. A naturally occurring TLR-4 antagonist, highly purified lipopolysaccharide (LPS) from Bartonella quintana, was first characterized using mouse macrophages and human dendritic cells (DCs). Mice with collagen-induced arthritis (CIA) and mice with spontaneous arthritis caused by interleukin-1 receptor antagonist (IL-1Ra) gene deficiency were treated with TLR-4 antagonist. The clinical score for joint inflammation, histologic characteristics of arthritis, and local expression of IL-1 in joints were evaluated after treatment.Results. The TLR-4 antagonist inhibited DC maturation induced by Escherichia coli LPS and cytokine production induced by both exogenous and endogenous TLR-4 ligands, while having no effect on these parameters by itself. Treatment of CIA using TLR-4 antagonist substantially suppressed both clinical and histologic characteristics of arthritis without influencing the adaptive anti-type II collagen immunity crucial for this model. Treatment with TLR-4 antagonist strongly reduced IL-1␤ expression in articular chondrocytes and synovial tissue. Furthermore, such treatment inhibited IL-1-mediated autoimmune arthritis in IL-1Ra ؊/؊ mice and protected the mice against cartilage and bone pathology.Conclusion. In the present study, we demonstrate for the first time that inhibition of TLR-4 suppresses the severity of experimental arthritis and results in lower IL-1 expression in arthritic joints. Our data suggest that TLR-4 might be a novel target in the treatment of rheumatoid arthritis.Rheumatoid arthritis (RA) is an autoimmune disease of unknown etiology associated with chronic inflammation of peripheral joints. Today it is generally accepted that proinflammatory cytokines play an important role in the pathogenesis of RA (1); however, the mechanisms of initiation and perpetuation of the inflammatory cascade in RA are still unknown.Toll-like receptors (TLRs) are a family of pattern recognition receptors that are involved in the recognition of conserved pathogen-associated molecular patterns (2). Ligand binding to TLRs initiates a signaling cascade that leads to the activation of the NF-B and interferon regulatory factor 3 transcription factors and MAPKs, which in turn promote the production of inflammatory cytokines, chemokines, and tissuedestructive enzymes and the expression of costimulatory molecules on antigen-presenting cells (APCs). These costimulatory molecules provide a second signal to T cells to initiate the adaptive immune response (3,4

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Antigen-presenting cells containing bacterial peptidoglycan in synovial tissues of rheumatoid arthritis patients coexpress costimulatory molecules and cytokines

Abstract: The results suggest that PG-containing cells may contribute to inflammation within the microenvironment of the joint in RA patients.

Cited by 90 publications

References 67 publications

Do Genetic Susceptibility, Toll-like Receptors, and Pathogen-associated Molecular Patterns Modulate the Effects of Wear?

Do Genetic Susceptibility, Toll-like Receptors, and Pathogen-associated Molecular Patterns Modulate the Effects of Wear?

Toll-like Receptor

Inhibition of toll‐like receptor 4 breaks the inflammatory loop in autoimmune destructive arthritis

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