Synovial fluid interleukin-8 and neutrophil function in rheumatoid arthritis and seronegative polyarthritis

Troughton, P. R.; Platt, R; Bird, H. A.; El-Manzalawi, E.; Bassiouni, Mohamed; Wright, V.

doi:10.1093/rheumatology/35.12.1244

Cited by 23 publications

(14 citation statements)

References 25 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…We have also shown that IL-8 stimulates DEK secretion. IL-8 is a major proinflammatory cytokine that has been implicated in the recruitment of macrophages, neutrophils, and macrophage-like synoviocytes to sustain an apparently autonomous cytokine network in the inflamed synovium and joint space of patients with inflammatory arthritis (22,59). Thus, the induction of DEK secretion by IL-8 is consistent with its chemoattractant function.…”

Section: Discussionmentioning

confidence: 98%

See 1 more Smart Citation

The DEK Nuclear Autoantigen Is a Secreted Chemotactic Factor

Mor‐Vaknin

Punturieri

Sitwala

et al. 2006

Molecular and Cellular Biology

134

View full text Add to dashboard Cite

The nuclear DNA-binding protein DEK is an autoantigen that has been implicated in the regulation of transcription, chromatin architecture, and mRNA processing. We demonstrate here that DEK is actively secreted by macrophages and is also found in synovial fluid samples from patients with juvenile arthritis. Secretion of DEK is modulated by casein kinase 2, stimulated by interleukin-8, and inhibited by dexamethasone and cyclosporine A, consistent with a role as a proinflammatory molecule. DEK is secreted in both a free form and in exosomes, vesicular structures in which transcription-modulating factors such as DEK have not previously been found. Furthermore, DEK functions as a chemotactic factor, attracting neutrophils, CD8؉ T lymphocytes, and natural killer cells. Therefore, the DEK autoantigen, previously described as a strictly nuclear protein, is secreted and can act as an extracellular chemoattractant, suggesting a direct role for DEK in inflammation.DEK is a mammalian oncoprotein and putative autoantigen whose primary biological function has not been previously elucidated, despite literature linking it to the regulation of transcription, chromatin architecture, and mRNA processing (1,2,11,15,16,24,35,51,65). The DEK protein is widely conserved among species and is transcribed at high levels, especially in hematopoietically derived cells (14,(62)(63)(64). DEK was first characterized as part of the protein product of the DEK-CAN fusion oncogene, resulting from a t(6;9) translocation found in a subset of patients with acute myelogenous leukemia (64). DEK is overexpressed in several different malignancies, including melanoma, hepatocellular carcinoma, glioblastoma, retinoblastoma, bladder cancer, T-cell large granular lymphocyte leukemia, and acute myelogenous leukemia independent of the t(6;9) translocation (7,10,19,20,29,30,32,39,64). Although DEK has previously been described as a strictly nuclear protein, DEK autoreactivity has been identified as a major component of the autoantibody profile in patients with juvenile idiopathic arthritis (JIA) and is also seen in patients with other autoimmune diseases (8,21,38,49,54,55). In the studies presented in this paper, we show that the nuclear protein DEK can be actively secreted by inflammatory cells, is found in synovial fluid samples from JIA patients, and can function as a chemoattractant for inflammatory cells, suggesting a potential role for DEK in immunity and/or autoimmunity. MATERIALS AND METHODSCell preparation. Monocyte-derived macrophages (MDM) were prepared as previously described (31). Briefly, heparinized venous blood samples were collected from healthy volunteers following a protocol approved by the institutional review board, and peripheral blood mononuclear cells were separated by FicollHypaque (Amersham Pharmacia Biotech AB, Uppsala, Sweden) density gradient centrifugation. MDM were purified by adherence to plastic for 2 h at 37°C at a concentration of 5 ϫ 10 5 /ml. Adherent cells were consistently Ͼ90% monocytes (31). Adherence-purified human mon...

show abstract

Section: Discussionmentioning

confidence: 98%

“…5A). As one of the major chemokines produced by synovial stromal cells, IL-8 plays an important role in attracting neutrophils and peripheral blood monocytes into the inflamed synovium (22,40,59,60), again suggesting a potential link between DEK secretion and inflammatory joint disease.…”

Section: Vol 26 2006 Dek Is a Secreted Chemotactic Factor 9489mentioning

confidence: 99%

The DEK Nuclear Autoantigen Is a Secreted Chemotactic Factor

Mor‐Vaknin

Punturieri

Sitwala

et al. 2006

Molecular and Cellular Biology

134

View full text Add to dashboard Cite

show abstract

“…In particular, proinflammatory cytokines including TNF‐α, IL‐1β, IL‐6 and IL‐17 amplify inflammation by inducing production of various additional inflammatory mediators and induction of recruitment, differentiation and proliferation of inflammatory cells. These inflammatory mediators are detectable in high concentrations in synovial fluid or serum of RA patients . Although some biologics targeting proinflammatory cytokines have improved the effectiveness of RA therapy , some patients are unresponsive to such therapy.…”

mentioning

confidence: 99%

Lipopolysaccharide accelerates collagen‐induced arthritis in association with rapid and continuous production of inflammatory mediators and anti‐type II collagen antibody

Tanaka¹,

Toki²,

Akimoto

et al. 2013

Microbiology and Immunology

View full text Add to dashboard Cite

Collagen-induced arthritis (CIA) is an animal model for rheumatoid arthritis (RA). Lipopolysaccharide (LPS) is known to accelerate CIA; however, the pathogenetic mechanisms are not yet fully understood. In this study, type II collagen (CII)-immunized mice were found to have marked increases in degree of expression of mRNA of inflammatory mediators such as tumor necrosis factor alpha (TNF-a), interleukin (IL)-1b, and macrophage inflammatory protein-2 (MIP-2) in their arthritic paws and of serum anti-CII antibody concentration before the onset of arthritis induced by LPS injection. The gene expression was rapid and continuous after direct activation of nuclear factor kB. The amounts of mRNA of TNF-a, IL-1b, and MIP-2, as well as of matrix metalloproteinases and the receptor activator of nuclear factor kB ligand, increased with the development of arthritis, correlated positively with clinical severity and corresponded with histopathological changes. Moreover, anti-TNF-a neutralizing antibody inhibited the development of LPS-accelerated CIA and a single injection of recombinant mouse TNF-a induced increases in anti-CII antibody concentrations, suggesting TNF-a may contribute to the development of arthritis by both initiation of inflammation and production of autoantibodies. These data suggest that exacerbation of RA by LPS is associated with rapid and continuous production of inflammatory mediators and autoantibodies.Key words anti-type II collagen antibody, collagen-induced arthritis, inflammatory mediators, lipopolysaccharide.Rheumatoid arthritis is a systemic autoimmune disease that is characterized by chronic inflammation of joints, leading to synovial hyperplasia, infiltration of leukocytes and progressive destruction of cartilage and bone (1). Various humoral factors are involved in the development of RA. One of these is autoantibodies, which activate complement systems by formation of immune complexes in combination with self-antigens and induce recruitment of inflammatory cells into synovium (1, 2). Another important factor is inflammatory mediators such as Correspondence Shinji Tanaka, Frontier Research Laboratories, Daiichi Sankyo Co., Ltd., 1-2-58 Hiromachi, Shinagawa-ku, Tokyo 140-8710, Japan. Tel: þ81 3 3492 3131; fax: þ81 3 5740 3644; email: tanaka.shinji.fv@daiichisankyo.co.jp List of Abbreviations: CIA, collagen-induced arthritis; CII, type II collagen; E. coli, Escherichia coli; GAPDH, glyceraldehyde-3-phosphate dehydrogenase; IkBa, inhibitor of nuclear factor kB alpha; IL, interleukin; LPS, lipopolysaccharide; LPS-CIA, lipopolysaccharide-accelerated collageninduced arthritis; MIP-2, macrophage inflammatory protein-2; MMP, matrix metalloproteinase; ND, not detected; NF-kB, nuclear factor kB; RA, rheumatoid arthritis; RANKL, receptor activator of nuclear factor kB ligand; SEM, standard error of the mean; TLR, Toll-like receptor; TNF-a, tumor necrosis factor alpha.

show abstract

“…Some of these are expressed in the synovial membrane and are present in the synovial fluid 2443 44 The response of pertussis toxin treated mast cells was reduced to all except one of the fluids (RD4), indicating the presence of chemotaxins mediating their effects through G i protein coupled receptors. Similarly, inhibition of tyrosine kinases reduced the response to several of the fluids, even to those that showed a decreased chemotactic activity on pertussis toxin treated cells.…”

Section: Discussionmentioning

confidence: 99%

Demonstration of mast cell chemotactic activity in synovial fluid from rheumatoid patients

Olsson

Ulfgren

Nilsson

2001

Annals of the Rheumatic Diseases

View full text Add to dashboard Cite

Objectives-The significance of the mast cell in the pathogenesis of rheumatic diseases has become more evident. Although mast cell hyperplasia is a feature of rheumatoid arthritis, the nature of mast cell chemoattractants involved in the recruitment of mast cells in joint diseases has not been studied in any detail. In this study the presence of mast cell chemotactic activity in synovial fluids was examined. Methods-Synovial fluids from seven rheumatoid patients were tested in a modified Boyden chamber, where a human mast cell line was used as responder. The presence of stem cell factor (SCF) and transforming growth factor (TGF ) was measured by enzyme linked immunosorbent assay (ELISA). Results-Six of the seven synovial fluids tested exhibited mast cell chemotactic activity. Two characterised human mast cell chemotaxins, SCF and TGF , were highly expressed in the synovium. Soluble SCF could be detected in all fluids analysed. Blocking antibodies against SCF or TGF almost completely blocked the activity in one fluid, partially blocked the activity in three, and did not aVect the activity in two. Treatment of the responder cells with pertussis toxin reduced the migratory response against seven fluids, indicating the presence of chemoattractants mediating their eVect through G i coupled receptors.Conclusion-These data demonstrate the presence of multiple factors in synovial fluid acting as mast cell chemoattractants, two of which are SCF and TGF that contribute to the eVect. These findings may be of importance for developing new strategies to inhibit mast cell accumulation in rheumatic diseases.

show abstract

Synovial fluid interleukin-8 and neutrophil function in rheumatoid arthritis and seronegative polyarthritis

Cited by 23 publications

References 25 publications

The DEK Nuclear Autoantigen Is a Secreted Chemotactic Factor

The DEK Nuclear Autoantigen Is a Secreted Chemotactic Factor

Lipopolysaccharide accelerates collagen‐induced arthritis in association with rapid and continuous production of inflammatory mediators and anti‐type II collagen antibody

Demonstration of mast cell chemotactic activity in synovial fluid from rheumatoid patients

Contact Info

Product

Resources

About