Attenuation of monosodium urate crystal-induced arthritis in rabbits by a neutralizing antibody against interleukin-8 (original) (raw)
Related papers
Rheumatoid factor and monosodium urate crystal-neutrophil interactions in gouty inflammation
Inflammation, 1981
A monolaycr system was designed to study the interactions between human neutrophils and monosodium uratc crystals important in gouty inflammation. The effects of rheumatoid factor on gouty inflammation were then examined in this system and in patients with acute gouty arthritis. Monosodium urate crystal phagocytosis was apparent at 30 rain, and this phagocytosis was accompanied by lysosomal enzyme release and decreased neutrophil adherence to plastic petri dishes. Rheumatoid factor did not affect phagocytosis, adherence, or lactic dcliydrogenasc release and appeared to variably enhance lysosomal enzyme release. Two of 19 acute gouty patients were found to have low titers of rheumatoid factor and, of these, one exhibited mild disease and the other tophaceous destructive disease.
Arthritis & rheumatology (Hoboken, N.J.), 2014
Monosodium urate monohydrate (MSU) crystal-induced interleukin-1β (IL-1β) secretion is a critical factor in the pathogenesis of gout. However, without costimulation by a proIL-1β-inducing factor, MSU crystals alone are insufficient to induce IL-1β secretion. The responsible costimulatory factors that act as a priming endogenous signal in vivo are not yet known. We undertook this study to analyze the costimulatory properties of myeloid-related protein 8 (MRP-8) and MRP-14 (endogenous Toll-like receptor 4 [TLR-4] agonists) in MSU crystal-induced IL-1β secretion and their relevance in gout. MRP-8/MRP-14 was measured in paired serum and synovial fluid samples by enzyme-linked immunosorbent assay (ELISA) and localized in synovial tissue from gout patients by immunohistochemistry. Serum levels were correlated with disease activity, and MSU crystal-induced release of MRPs from human phagocytes was measured. Costimulatory effects of MRP-8 and MRP-14 on MSU crystal-induced IL-1β secretion fr...
Annals of The Rheumatic Diseases, 1985
Gout and classical rheumatoid arthritis rarely coexist. We report a patient with strong evidence for both these diseases. Possible reasons for the negative correlation between these diseases are summarised. One hypothesis suggests inhibition of surface activity of monosodium urate crystals (MSU) by binding of rheumatoid factor (RF). This was studied with a purified monoclonal rheumatoid factor (mRF) with specificity for IgG. The mRF bound preferentially to MSU coated with IgG in contrast with the IgM control. Inhibition of the neutrophil chemiluminescence (CL) response to IgG-coated MSU was observed at concentrations of mRF that had no effect on the CL response to uncoated crystals. Neutrophil activation was not altered by coating crystals with an IgM control at the same concentration. These data suggest that RF may bind to antigenic determinants on exposed Fc of adsorbed IgG and block the interaction of crystal-bound IgG with Fc receptors. Although crystal coating by RF may modify the expression of gouty arthritis, it is unlikely to be the sole explanation for the dissociation between gout and RA.
Activation of human fibroblast-like synoviocytes by uric acid crystals in rheumatoid arthritis
Cellular & molecular immunology, 2011
Hyperuricemia-mediated uric acid crystal formation may cause joint inflammation and provoke the destruction of joints through the activation of inflammasome-mediated innate immune responses. However, the immunopathological effects and underlying intracellular regulatory mechanisms of uric acid crystal-mediated activation of fibroblast-like synoviocytes (FLS) in rheumatoid arthritis (RA) have not been elucidated. Therefore, we investigated the in vitro effects of monosodium urate crystals, alone or in combination with the inflammatory cytokines tumor-necrosis factor (TNF)-α or interleukin (IL)-1β, on the activation of human FLS from RA patients and normal control subjects and the underlying intracellular signaling mechanisms of treatment with these crystals. Monosodium urate crystals were able to significantly increase the release of the inflammatory cytokine IL-6, the chemokine CXCL8 and the matrix metalloproteinase (MMP)-1 from both normal and RA-FLS (all P<0.05). Moreover, the ...
Feasibility of a Strategy to Prevent Gouty Arthritis Through Limiting Crystallization of Monosodium
2018
Background: Crystallization of monosodium urate (MSU) is the cause of gout as well as is the cause of about 10% of kidney stones. The focus of this paper is on altering the crystallization of MSU, which occurs in the affected joint space. It is generally accepted that the inflammation caused by the MSU crystals leads to the clinical signs of gout: swelling, redness, and pain. Developing treatment and prevention strategies are hampered by not knowing the exact mechanisms. It is known, however, that the inflammatory phase can be controlled by limiting the size and amount of crystals formed. It is also known that only 2 to 36% of hyperuricemic individuals get gout; suggesting that there are chemicals found in the body that can prevent or limit crystallization in hyperuricemic individuals. This study was designed to look at the ability of various chemicals to modify the crystallization of MSU. Methods and Findings: It was found that vitamins (riboflavin, pyridoxine HCL, and β-carotene),...
Arthritis Research & Therapy, 2012
Introduction: Monosodium urate monohydrate (MSU) crystals synergize with various toll-like receptor (TLR) ligands to induce cytokine production via activation of the NOD-like receptor (NLR) family, pyrin domain-containing 3 (NLPR3) inflammasome. This has been demonstrated in vitro using human cell lines or monocytes of healthy volunteers. In the present study, we have investigated the effect of MSU crystals and of their combination with TLR ligands in peripheral blood mononuclear cells (PBMC) of patients with gout. Methods: PBMCs from 18 patients with primary gout and 12 healthy donors were exposed to MSU crystals in the presence or absence of saturated fatty acid C18:0 (free fatty acid, TLR2 ligand), palmitoyl-3-cystein (Pam 3 Cys, TLR1/2 ligand) and fibroblast stimulating factor-1 (FSL-1, TLR 2/6 ligand). Production of IL-1β, IL-6, IL-8, IL-17 and tumor necrosis factor alpha (TNFα) was determined by ELISA. mRNA transcripts of IL-1β were measured by real-time PCR.
Arthritis Research & Therapy, 2013
Introduction: Monosodium urate crystals (MSU), the etiological agent of gout, are one of the most potent proinflammatory stimuli for neutrophils. The modulation of MSU-induced neutrophil activation by inhibitory receptors remains poorly characterized. The expression of the myeloid inhibitory C-type lectin-like receptor (MICL) in neutrophils is downregulated by several proinflammatory stimuli, suggestive of a role for this receptor in neutrophil function. We thus investigated the potential role of MICL in MSU-induced neutrophil activation. Methods: The expression of MICL was monitored in human neutrophils by flow cytometry and Western blot analysis after stimulation with MSU. Protein tyrosine phosphorylation was also assessed by Western blot analysis and the production of IL-1 and IL-8 by enzyme-linked immunosorbent assay. Changes in the concentration of cytoplasmic free calcium were monitored with the Fura-2-acetoxymethyl ester calcium indicator. MICL expression was modulated with an anti-MICL antibody in neutrophils and siRNA in the PLB-985 neutrophil-like cell line. Results: MSU induced the downregulation of MICL expression in neutrophils. A diminution in the expression of MICL induced by antibody cross-linking or siRNA enhanced the MSU-dependent increase in cytoplasmic calcium levels, protein tyrosine phosphorylation and IL-8 but not IL-1 production. Pretreatment of neutrophils with colchicine inhibited the MSU-induced downregulation of MICL expression.