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We examined the ability of rIL-13 to regulate rIL-lα induced IL-1β, IL-1 receptor antagonist (IL-1ra) and IL-8 production in cultured peripheral blood mononuclear cells (PBMC), endothelial cells and fibroblasts. Furthermore, we examined whether rIL-13 could influence the production of the arachidonic acid products LTB4, 12-HETE and 15-HETE by PBMC. rIL-1α-stimulated PBMC cultures secreted high levels...
Madimadi, a Korean folk medicine, has been applied to treat rheumatoid arthritis (RA). However, its mechanisms of action have not been examined. The involvement of inflammatory cytokines, particularly TNF-α, IL-1β, and IL-8, resulting in local inflammation in the pathogenesis of RA is now widely accepted. Madimadi dose-dependently inhibited TNF-α, IL-1β, and IL-8 production from activated human mast...
To determine the contribution of IL-1, TNF-α and IL-17 on AP-1, NF-κB and Egr-1 activation in cytokine induced bone destruction as observed in rheumatoid arthritis, we investigated the effect of these pro-inflammatory cytokines used alone or in combination on transcription factor activation in osteoblast-like ROS 17/2.8 cells. The effects of each cytokine were measured by RT-PCR and immunocytochemistry...
Rheumatoid arthritis is a common debilitating disease. Chronic joint inflammation leads to irreversible joint damage. Disability is a common sequel, therefore it is a major healthcare burden. Treatment by convention disease modifying anti-rheumatic drugs improves symptoms and signs but does not improve long-term prognosis. Tumour necrosis factor alpha is a powerful pro-inflammatory cytokine. Blocking...
Patients with rheumatoid arthritis (RA) treated with anti-tumor necrosis factor (TNF) strategies have an increased susceptibility to infections, especially those caused by intracellular pathogens. In this study we assessed the cytokine production capacity in patients with RA and we further investigated whether anti-TNF therapy modulates the production of pro-inflammatory cytokines involved in the...
Collagen-induced arthritis (CIA) is a widely used model of human rheumatoid arthritis (RA) characterized by chronic inflammation of the synovial joints. The pathogenesis of RA and CIA has not been completely defined, but both involve the recruitment of leukocytes and lymphocytes to the joints and Th1-type cell mediated autoimmune responses. The C–C chemokine receptor 5 (CCR5) is preferentially expressed...
Rheumatoid arthritis (RA) is a complex heterogeneous disease with an estimated genetic contribution to of 30–50%. Approximately one third arises from the major histocompatibility complex (MHC) at 6p21.3. The contribution of specific DRB1 alleles encoding the shared epitope has been well described, however, several recent studies have suggested that additional telomeric genetic influences may exist...
Cytokine medicines have been licensed for the treatment of rheumatoid arthritis since 2000. The rheumatology community has accrued a large amount of experience in the use of these medications. This experience has led to the development of guidelines for their use that include ongoing vigilance for long term adverse events and efficacy using the Biologics Register. Delivery of these expensive therapies...
TNFα and IL-1 are the pivotal cytokines involved in rheumatoid arthritis (RA). More recently, the biological therapy targeting TNFα or IL-1 has been impressively effective for many RA patients, however, it remains insufficient in some patients. In the present study, we examined the combined effects of two agents against TNFα and IL-1 in human RA synovial membrane. Synovial explants (an ex vivo model)...
The purpose of this open pilot study was to assess possible mechanisms of the effects of leflunomide by studying the influence of the drug on the serum levels of MMP-1, MMP-3, IL-10, IL-6 and their possible correlation with clinical disease parameters.Thirty patients with long standing active rheumatoid arthritis were enrolled in this study. All patients failed at least 5 DMARDs in the past and were...
Cytokines which are produced by host cells play an important role in pathogenesis both rheumatoid arthritis (RA) and chronic periodontitis (CP). In this study, we aim to investigate the levels of Interleukin (IL)-4 and IL-10 in gingival crevicular fluid (GCF). Seventeen patients with CP, 17 patients with RA and 17 healthy controls (HC) were included. The RA group was divided into two groups according...
Adiponectin has been shown to exert insulin-sensitizing, anti-atherogenic, and anti-inflammatory properties in metabolic diseases. It has been suggested that adiponectin may play a role in rheumatoid arthritis (RA). To assess adiponectin in serum and synovial fluid from patients with RA and osteoarthritis (OA), and in serum from healthy controls. Adiponectin and CRP levels were analyzed by ELISA....
Macrophage migration inhibitory factor (MIF) is clearly associated with rheumatoid arthritis (RA) disease severity. However, the regulation of MIF during the course of RA has not been subjected to similar scientific scrutiny. The aim of our study was to investigate the role of various Toll-like receptors (TLRs) and inflammatory mediators on MIF production by dendritic cells (DCs) in healthy controls...
Interleukin 15 (IL-15) is a pleiotropic pro-inflammatory cytokine known to play a relevant role in rheumatoid arthritis (RA) pathogenesis. In this study we aimed to investigate for the first time the contribution of IL15 gene to RA susceptibility. We screened 13 single nucleotide polymorphisms (SNPs) localised within IL15 regulatory regions (promoter, 5′ UTR region and 3′ UTR region) in a total of...
To elucidate the role of the synovium in bone destruction by osteoclasts in rheumatoid arthritis (RA), primary synovial cells isolated from RA patients were cultured and characterized. The cultured primary cells did not produce RANKL (TRANCE/ODF/OPGL/TNFSF11/CD254), an inducer of osteoclast differentiation, but constitutively produced its inhibitor, osteoprotegerin (OPG). Addition of TNF-α to the...
Fibroblast-like synoviocytes (FLS) play a major role in the pathogenesis of rheumatoid arthritis (RA). FLS isolated from patients with RA (FLS-RA) express B cell-activating factor belonging to the TNF family (BAFF), a cytokine that has been associated with the onset and progression of RA. Glucocorticoids are powerful anti-inflammatory drugs used in the treatment of RA. In the present study, we examined...
Although a notable amount of CCL20 is detectable in the synovial fluid of human rheumatoid arthritis (RA), its role in the pathogenesis of RA remains to be determined. IL-1β vigorously induced the production of CCL20 from FLSs of human RA and the production of CCL20 induced by TNF-α was partially attributed to a trace amount of IL-1β induced by TNF-α. Although IL-6 failed to induce CCL20, TNF-α-induced...
Background: The therapeutic effect of TNFα inhibition in rheumatoid arthritis (RA) is accompanied by an altered peripheral T cell cytokine profile, but the underlying mechanisms are not well known. In CD4+ T cells, TNF signalling includes the p38 MAP kinase (MAPK) pathway, which is also involved in proliferation and production of IL-4 and IFNγ. Methods: Phosphorylation of p38 MAPK was analysed flow...
Although physical therapy has been shown to be an effective method for treatment of rheumatoid arthritis, a thorough investigation on the impact of mechanical signals upon the complex cytokine network associated with pathogenesis has not yet been conducted. In the current study, our research group investigated the effect of mechanical stimulation on primary and immortalized rheumatoid arthritis synovial...
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