Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0003864 (arthritis)
 69,039 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The levels of alpha1-proteinase inhibitor-elastase and alpha 2-macroglobulin (alpha 2M)-proteinase complexes were measured in synovial fluids from arthritis patients by use of specific immunosorbent assays. Both types of proteinase inhibitor-proteinase complexes were significantly correlated with each other as well as with the total neutrophil count in synovial fluids of rheumatoid arthritis patients but were discordant in synovial fluids of patients with osteoarthritis. One synovial fluid sample showed active (inhibitory) alpha 2M as well as active collagenase. We purified alpha 2M from pooled synovial fluids obtained from patients with rheumatoid arthritis. This alpha 2M retained approximately 90% of its proteinase binding (inhibiting) capacity, compared with that of normal plasma alpha 2M. We found no evidence that alpha 2M was inactivated by means other than proteinases.
Arthritis Rheum 1986 Mar
PMID:Alpha 2-macroglobulin-proteinase complexes as correlated with alpha 1-proteinase inhibitor-elastase complexes in synovial fluids of rheumatoid arthritis patients. 242 37

An understanding of the immunologic relationships between collagenases of various cellular origins is necessary to define the roles of various cell types in the pathologic tissue destruction seen in chronic inflammatory diseases, such as rheumatoid arthritis. We compared the immunologic cross-reactivity of human neutrophil and skin fibroblast collagenases, utilizing polyclonal antisera prepared to purified enzymes. Polyclonal antisera from rabbits immunized with neutrophil collagenase recognized fibroblast collagenase, as well as the neutrophil enzyme, when analyzed by immunoblot techniques. The cross-reactive epitopes constituted a major proportion of the antibody population, as shown by competitive inhibition enzyme-linked immunosorbent assay; 50% of the antibody to neutrophil collagenase was inhibited by skin collagenase. Paradoxically, antisera to fibroblast collagenase failed to recognize the neutrophil enzyme, either by immunoblot techniques or competitive inhibition enzyme-linked immunosorbent assay, an observation which supports the notion that there are unique immunodominant epitopes. The cross-reactivity with skin fibroblast collagenase shown by the neutrophil antibody suggests a conservation of epitopes between collagenases of different cellular origins. The presence of epitopes unique for each enzyme, however, could lead to a feasible approach for investigating the differential contribution of various cell types to collagenolytic activity in inflamed tissues.
Arthritis Rheum 1987 Jun
PMID:The immunologic relationship of human neutrophil and skin collagenases. 244 Apr 53

A T cell line specific to human type II collagen (CII) was selected and propagated from DBA/1J mice immunized with human CII. The line cells were not reactive to type I or type III collagen of human origin, but they were cross-reactive to bovine, rat, and rabbit CII and they recognized both native and heat-denatured human CII. The cells were reactive to an N-terminal three-quarters fragment of human CII, produced by tadpole collagenase digestion of human CII, but not to a C-terminal one-quarter fragment of human CII. The cells showed Thy-1+, Lyt-1+, Lyt-2-, and L3T4+ phenotypes characteristic of T helper cells or delayed-type hypersensitive cells, determined by the immunofluorescence method. To clarify the role of T cells in the pathogenesis of collagen-induced arthritis, we inoculated this cell line into DBA/1J mice and found that they developed clinical arthritis, albeit at a low incidence. The cells attenuated by x-ray were capable of inducing resistance to the subsequent induction of collagen-induced arthritis of DBA/1J mice. The sera from mice protected by inoculation of the cell line exhibited anti-idiotypic antibody response against conventional and monoclonal anti-CII antibodies. Anti-T cell receptor response may be involved in the mechanism for the protective effect of the cell line against autoimmune murine arthritis.
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PMID:Isolation of T cell line capable of protecting mice against collagen-induced arthritis. 244 73

The biological effects of tumor necrosis factor (TNF) include the enhancement of fibroblast proliferation, the secretion of collagenase and prostaglandin E2 (PGE2) by fibroblasts, and the resorption of bone and cartilage, suggesting a role for this cytokine in arthritic conditions. To investigate this, we measured the levels of TNF in synovial fluids and evaluated its secretion by synovial fluid mononuclear cells and tissues from patients with rheumatoid arthritis, osteoarthritis, and seronegative arthritis and normals. TNF was found to be secreted in all arthritic conditions but not in normals. The levels of TNF were highest in synovial fluid and correlated with interferon-gamma (IFN-gamma) levels but not PGE2. The production of TNF was stable in a single joint for 3 to 6 months. Using immunohistochemical staining, TNF was localized to mononuclear cells in the lining layer, sublining, and perivascular areas of synovial tissue. The secretion of TNF by rheumatoid synovial fluid mononuclear cells was inhibited by PGE2, while IFN-gamma enhanced its production in those cells which were spontaneously secreting TNF. Our data suggest that TNF may play a role in various arthritic diseases.
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PMID:Characteristics of tumor necrosis factor production in rheumatoid arthritis. 247 44

Cellular interactions involved in the chronic inflammatory response, characteristic of those found in the joints of rheumatoid arthritis patients, were investigated by examining the effect of interleukin-1 (IL-1), tumor necrosis factor alpha, and gamma-interferon on the regulation of IL-1 gene expression and production by synovial fibroblasts. Biologically active IL-1 was detected in lysates of IL-1-treated rat and human fibroblasts that had been isolated from synovial tissue by collagenase digestion. Northern blot analysis of RNA isolated from these cells revealed the expression of IL-1 alpha and IL-1 beta transcripts. Neither the IL-1 transcripts nor the biologic activity of IL-1 was found in untreated synovial fibroblasts. The messenger RNA induction in synovial cells was followed by a time- and dose-dependent expression of intracellular IL-1 activity. Human monocytes and human skin fibroblasts also responded to IL-1 treatment by producing IL-1-specific transcripts. These observations suggest that IL-1 plays a key role in stimulating immune and inflammatory responses and in sustaining those responses through continued production at sites of inflammation.
Arthritis Rheum 1989 Mar
PMID:Interleukin-1 induces interleukin-1 alpha and interleukin-1 beta gene expression in synovial fibroblasts and peripheral blood monocytes. 249 10

IL-1 and prostaglandin (PGE2, PGF2 alpha, TXB2) concentrations, PLA2 activity, neutral protease activity, and collagenase activity specific for types I and II collagen were determined in the SF of patients suffering from RA, before and after treatment with TA. Active and latent forms of protease and collagenases were regularly detected but were unrelated to IL-1, PLA2, and PGE2. TA induced a significant decrease in tested eicosanoids but IL-1, PLA2, and proteases were unchanged.
Semin Arthritis Rheum 1989 Feb
PMID:Effects of tiaprofenic acid on interleukin 1, phospholipase A2 activity, prostaglandins, neutral protease, and collagenase activity in rheumatoid synovial fluid. 254 31

The prophylactic effect of glycosaminoglycan polysulfuric acid ester (GAGPS) on cartilage lesions was studied using the Pond-Nuki model of canine osteoarthritis. Starting 2 days after anterior cruciate transection, GAGPS or saline was administered intraarticularly twice weekly for 4 weeks. After 4 weeks, gross and histologic medial femoral condylar lesions had developed to a lesser degree in GAGPS-treated dogs than in saline-treated dogs. The uronic acid and hydroxyproline levels in cartilage were significantly higher in the GAGPS-treated dogs than in the saline-treated dogs. Levels of active and latent collagenase in the cartilage of GAGPS-treated dogs were lower than in the cartilage of saline-treated dogs. With GAGPS treatment, swelling of the cartilage, an indicator of collagen network integrity, remained near control levels. Although increased synthesis of proteoglycan and collagen may account for some of these results, we propose that one mechanism of action of GAGPS is its ability to decrease collagen degradation, either by decreasing the synthesis of collagenase or by directly inhibiting the production of collagenase in cartilage.
Arthritis Rheum 1989 Jun
PMID:Prophylactic treatment of canine osteoarthritis with glycosaminoglycan polysulfuric acid ester. 254 87

Ro 23-6457, (all-E)-3,7-dimethyl-9-[2-(trifluoromethyl)-6-(nonyloxy)phenyl]-2, 4,6,8- nonatetraenoic acid, and Ro 23-2895, (all-E)-9-[2-(nonyloxy)phenyl]-3,7-dimethyl-2,4,6,8-nonatetraen oic acid, are two novel retinoid analogs which exhibit antiinflammatory activity in both the developing and the established rat adjuvant arthritis models [8]. Here we investigated the effect of these two compounds on the production of arachidonic acid (AA) metabolites in two in vitro test systems [i.e., Ca2+ ionophore A23187 (I)-stimulated resident rat peritoneal macrophages (MO) and cytokine-stimulated human dermal fibroblasts (HDF)]. Both compounds, Ro 23-6457 and Ro 23-2895, significantly inhibited the release of 14C-AA metabolites and the production of LTB4, PGE2, and 6-keto-PGF1 alpha in I-stimulated MO, at concentrations of 1-33 microM. Both compounds also inhibited the production of PGE2 in HDF stimulated by either rhuIL-1 alpha or huTNF alpha at concentrations of 1 x 10(-5) to 1 x 10(-7) M. Ro 23-2895 was also a potent inhibitor of IL-1-induced collagenase production in rheumatoid synovial cells (IC50 approximately 1 to 2.5 x 10(-8) M). The inhibitory profile of these novel compounds in these cell systems is therefore similar to that of other known antiinflammatory retinoids (e.g., all-trans- and 13-cis-retinoic acid). Inhibitory effects such as those described here might in part contribute to the antiinflammatory activity of these compounds in vivo.
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PMID:In vitro inhibition of arachidonic acid metabolism by two novel retinoid analogs. 255 63

Interleukin-1 (IL-1) may contribute to tissue destruction in rheumatoid arthritis, in part, by inducing messenger RNA (mRNA) that encodes interstitial collagenase. In human synovial fibroblasts in vitro, IL-1 induced collagenase mRNA accumulation 6 hours after being added to the cells. High levels of mRNA remained present for at least 48 hours after treatment. The rate of transcription of collagenase in isolated nuclei peaked after approximately 6 hours of treatment with IL-1 and declined thereafter, becoming nearly undetectable by 24 hours. The persistence of mRNA, in view of the transient peak of transcription, suggested that collagenase mRNA was stable in synovial fibroblasts. The half-life of collagenase mRNA after the synoviocytes were treated with actinomycin D was approximately 27 hours, both in the presence and in the absence of IL-1. It has been noted that induction of the expression of collagenase by phorbol esters requires fos protein synthesis and is mediated through a tetradecanoyl phorbol acetate response element in the 5'-flanking region of the gene. However, we found that cycloheximide, when added to synovial fibroblast cultures up to 6 hours after treatment with IL-1, inhibited the expression of collagenase mRNA. These results suggest that fos alone is unlikely to be sufficient for collagenase expression, and that additional factors, or alternative pathways, are involved in the induction of collagenase by IL-1.
Arthritis Rheum 1989 Dec
PMID:Regulation of human synovial fibroblast collagenase messenger RNA by interleukin-1. 255 44

Autoimmunity to collagen was investigated in several naturally occurring arthropathies of the dog. Increased levels of serum anti-native collagen type II antibody, as assessed by ELISA, were shown in 72.4% of dogs with rheumatoid arthritis (RA), 88% of dogs with infective arthritis (IA) and 52% of dogs with osteoarthritis (OA) (p less than 0.001). The mean levels of antibody in cruciate disease patients (CR) were also significantly increased compared to control dogs (p less than 0.01). Serum anti-collagen antibody in OA dogs correlated with that in precipitated serum immune complexes. There was also a correlation between anti-collagen antibody level in synovial fluid and in synovial fluid complexes in dogs with rupture of the cranial cruciate ligament. In all patient groups, collagenase digestion of polyethylene glycol (PEG) precipitates from sera and synovial fluids caused a significant rise in specific antibody levels to collagen, indicating the presence of collagen-anti-collagen complexes in all arthropathies. In dogs with RA, the levels of collagen-specific antibody in synovial fluid complexes correlated with the total IgG in these complexes. These findings implicate collagen-anti-collagen complexes in the pathogenesis of naturally occurring joint diseases in the dog, but they are unlikely to be the primary aetiological mechanism.
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PMID:Anti-type II collagen antibody in naturally occurring canine joint diseases. 259 Aug


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