Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0003873 (rheumatoid arthritis)
 53,068 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Inflammatory and 'non-inflammatory' forms of arthritis affect a large proportion of the population and these diseases can often lead to disability. Although the pain of arthritis can be relieved to some extent by the peripherally acting aspirin-like drugs, the progression of disease leading to joint destruction is largely resistant to current drug therapy. The synovial joints of patients with rheumatoid arthritis are infiltrated with neutrophils, macrophages and lymphocytes and the resident cells become activated to degrade the cartilage and bone. The inflammatory and destructive changes that occur are brought about by the action of mediators or local hormones which are produced by a variety of cell-types. Lipid mediators, such as prostaglandins, contribute to the symptoms of arthritis while polypeptide cytokines, such as interleukin 1 and tumour necrosis factor, play a key role in joint destruction by activating the synovial cells and chondrocytes to release metalloproteinases, such as collagenase. Aspirin-like drugs inhibit the production of prostaglandins from inflamed tissues and thereby blunt the symptoms of arthritis. However, these drugs do not suppress the production of collagenase from connective tissue cells and, therefore, do not halt the degeneration of joint tissues.
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PMID:Pathogenesis and treatment of chronic arthritis. 269 74

We found the presence of collagenase-like (CL) peptidase in synovial fluid by a highly sensitive fluorescence assay using (succinyl-Gly-Pro-Leu-Gly-Pro)-4-methyl-coumaryl-7-amide (Suc-GPLGP-MCA) as a substrate. Suc-GPLGP-MCA is hydrolyzed at the Leu-Gly bond by CL-peptidase. The CL-peptidase activity in synovial fluid was significantly higher in patients with rheumatoid arthritis (RA) than in patients with osteoarthritis (OA) and in arthropathy-free controls. No significant difference in CL-peptidase activity in synovial fluid was found between patients with OA and arthropathy-free controls.
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PMID:Collagenase-like (CL) peptidase activity in synovial fluid from patients with rheumatoid arthritis. 283 60

Native serum C1q, the collagenous-like subcomponent of the first component of complement, is not recognized by polyclonal anti-collagen type II antibodies. However, when purified C1q was subjected to limited proteolysis by collagenase it showed antigenic cross-reactivity with collagen type II. The same cross-reactivity was observed with hemolytically active C1q in synovial fluids of patients with rheumatoid arthritis (RA), whereas C1q from synovial fluids of patients with osteoarthritis (OA), villo-nodular synovitis and ankylosing spondylitis was not recognized by this antibody. However, incubation of synovial fluid C1q of OA patients with synovial fluid leucocytes from RA patients led to an alteration of OA-C1q which was now recognized by the anti-collagen type II antibody.
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PMID:Enzymatic alteration of C1q, the collagen-like subcomponent of the first component of complement, leads to cross-reactivity with type II collagen. 283 Jan 44

We studied synovial fluid (SF) collagenase in 10 women with severe rheumatoid arthritis (RA), 10 with pyrophosphate arthropathy, and 10 with idiopathic destructive disease of the shoulder conforming to a pattern recently described. SF cell counts were highest in the RA group. Particles were detected by polarized light microscopy and alizarin red staining. Crystals were seen in fluids from all 3 groups; pyrophosphate predominated in the pyrophosphate arthropathy group and alizarin red-positive particles in the idiopathic disease group. Collagenase and tissue inhibitor of metalloproteinase levels were estimated in SF after gel filtration. Tissue inhibitor of metalloproteinase activity was detected in all fluids, but tended to be highest in the RA group. Collagenase activity was detected in 3 RA fluids only. In no sample was collagenase found in an active form. These findings support the clinical concept of an aggressive destructive process which sometimes occurs in the shoulder joints of elderly women. Because we were not able to detect free collagenase in SF from any of the patients with idiopathic shoulder disease, the data suggest that high levels of active collagenase are not characteristic of this group of patients.
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PMID:Synovial fluid collagenase in patients with destructive arthritis of the shoulder joint. 284 85

The activities of collagenase-like peptidase, estimated by using (succinyl-Gly-Pro-Leu-Gly-Pro-Leu-Gly-Pro)-4-methylcoumaryl-7-amide as substrate, and of dipeptidyl-aminopeptidase IV were decreased in the sera from patients with rheumatoid arthritis. Both enzymes bring about the degradation of peptides derived from collagen. A significant positive correlation was observed between the activities of the two serum peptidases.
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PMID:Collagenase-like peptidase activity in serum from patients with rheumatoid arthritis. 285 19

Long-term synovial fibroblast cultures were exposed to interleukin 1 (IL-1) or prostaglandin E2 (PGE2). The normally spindle-shaped fibroblasts changed to stellate-shaped cells, resembling the HLA-DR-positive, collagenase-producing cells which are normally seen only in primary cultures from enzyme-digested rheumatoid synovial tissue. However, the IL-1- or PGE2-induced fibroblasts were not HLA-DR-positive. This suggests that these cell populations represent originally different cell lines or that the expression of HLA-DR antigens is not induced by the agents used. For further characterization of these stellate cells, the location of fibronectin and type I collagen was studied by specific antibodies and the pericellular coat around fibroblasts was visualized by the erythrocyte exclusion method. Both IL-1 and PGE2 treatments destroyed the intercellular fibronectin network. Type I collagen was detected as intracellular granules. The stellate fibroblasts were usually full of these granules in contrast to intact fibroblasts in which the number of collagen fluorescence granules varied greatly. The pericellular coat known to be formed mainly by hyaluronic acid was similar around spindle and stellate-shaped fibroblasts. Rheumatoid arthritis-derived fibroblasts did not differ from their non-rheumatoid counterparts in any of the experiments. The effect of IL-1 and PGE2 on fibroblasts simulates the interaction between mononuclear cells and fibroblasts in synovial stroma and also potentially the interactions between different cell types in synovial lining.
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PMID:Connective tissue components in synovial fibroblast cultures exposed to interleukin 1 and prostaglandin E2. 287 May 82

Using monoclonal antibodies, we examined the display of rabbit Ia by articular chondrocytes. We found that 29 to 46% of chondrocytes displayed Ia antigen compared with 46 to 60% of spleen cells. Ia antigen expression was not likely to be the result of enzyme treatment. To investigate antigen presenting activity of enzyme dissociated normal articular chondrocytes, adult rabbits were immunized in the front foot pads with ovalbumin (OVA) in complete Freund's adjuvant. Four to six weeks later, draining popliteal lymph node cells (LNC) were obtained. Articular chondrocytes were obtained by overnight collagenase, DNase, and hyaluronidase digestion of cartilage from both ends of femurs and proximal end of tibias. Antigen-presenting cells from spleen were used as positive controls. LNC and nylon wool-purified T cells were cultured with OVA pulsed and mitomycin C-treated chondrocytes or spleen cells, and lymphocyte proliferation was measured by 3H-TdR uptake. Both chondrocytes and spleen cells showed antigen presenting activity, and stimulation of lymphocyte proliferation was inhibited by murine monoclonal anti-rabbit Ia antibody (2C4), whereas control plasmacytoma cell supernatants had no effect. When T cells were purified first by Sephadex G-10 and later by nylon wool columns, these cells were dependent on antigen-presenting cells for immunogen (OVA)-induced lymphocyte proliferation. Again, chondrocytes under these strict experimental conditions presented antigen to T cells. Chondrocytes also stimulated autologous and allogeneic normal lymphocytes. Thus, normal chondrocytes have Ia antigens on their surface and can function as antigen-presenting cells. These results are significant for the understanding of local cellular interaction in the pathogenesis of rheumatoid arthritis.
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PMID:Class II histocompatibility antigen-mediated immunologic function of normal articular chondrocytes. 293 76

Interleukin-1 (IL-1) is the name given to the polypeptides produced by activated mononuclear phagocytes which were originally defined as lymphocyte activating factors (LAF). Administration of IL-1 in vivo causes fever and synthesis of acute phase proteins. In vitro they have been shown to cause cartilage and bone resorption, and to stimulate fibroblasts and chondrocytes to make prostaglandins and latent collagenase. IL-1 has therefore been proposed to be an important inflammatory mediator and may be involved in the destruction of cartilage and bone that is a feature of rheumatoid arthritis and other inflammatory diseases of joints. We therefore looked for IL-1 receptors on connective tissue cells which might be targets for therapeutic intervention. Here we report the iodination, to high specific activity and with retention of full biological potency, of the two types of natural porcine IL-1. These ligands have been used to demonstrate high affinity dissociation constant (approximately 10(-10) M) specific binding sites on pig chondrocytes and synovial fibroblasts, human dermal fibroblasts and murine osteoblasts (3,000-5,000 sites per cell). Most interestingly, the two different Il-1 proteins show a similar affinity for a common class of receptors.
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PMID:Identification of a common class of high affinity receptors for both types of porcine interleukin-1 on connective tissue cells. 294 58

The number of leucocytes and the concentrations of protein, proteoglycans (PG), elastase a1 proteinase inhibitor complexes (E-alpha 1 Pi) and collagenolytic activity were measured in the synovial fluid (SF) of 15 patients with rheumatoid arthritis (RA) and 18 with osteoarthritis (OA). The mean levels of protein, E-alpha 1 Pi and collagenase and the number of leucocytes were higher in RA than in OA SF. However, the mean level of PG was higher of OA SF than in RA. In the latter, they were principally in the form of monomers and fragments while in the former they were in the form of aggregates and monomers. There was a direct relationship between the concentration of E-alpha 1 Pi and either the number of white cells or the concentration of synovial proteins, suggesting that the measurement of E-alpha 1 Pi complexes is a biochemical index of the local inflammatory reaction. There was an inverse correlation between the concentrations of PG and E-alpha 1 Pi which may reflect the effect of degradation in PG of elastase and other enzymes released at the same time. Finally, there was a direct relationship between the concentration of E-alpha 1Pi and collagenase which may be the reflection of a simultaneous release of various enzymes from leucocytes and macrophages.
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PMID:Measurement of proteoglycans, elastase, collagenase and protein in synovial fluid in inflammatory and degenerative arthropathies. 298 25

Human PHA-stimulated mononuclear cells produce a factor which inhibits synovial cell collagen and non-collagen protein synthesis, whereas it enhances hyaluronic acid (HA) production. Indomethacin (10(-4)-10(-6) M), a cyclo-oxygenase inhibitor, suppresses this effect, suggesting that the mechanism is prostaglandin-mediated. The active material, of apparent molecular weight 12 000-20 000, also displays the properties of the mononuclear cell factor (MCF) previously described by others, since its stimulates collagenase and PGE2 release by the cultured synovial cells. Furthermore, it co-purifies with interleukin 1 (IL 1) as shown by lymphocyte-activating factor activity. This strongly suggests that IL 1 could be responsible for some (or all) the effects observed on MCF-exposed synovial cells. From these data, we deduce the possibility that mononuclear cells may participate in limiting synovial collagen deposition in rheumatoid arthritis.
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PMID:Mononuclear cell-mediated modulation of synovial cell metabolism. I. Collagen synthesis. 298 10


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