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)

Circulating hyaluronan originating from the synovial membrane and circulating proteoglycan released from cartilage were determined by specific assays in patients with osteoarthritis (OA), rheumatoid arthritis (RA), reactive arthritis or juvenile chronic arthritis (JCA). Elevated hyaluronan concentrations were found in OA and RA, suggesting proliferation of the synovial membrane in both diseases. The proteoglycan concentrations were highest in OA and polyarticular JCA indicating increased turnover of cartilage matrix. The concentrations of the macromolecules did not correlate except in the group with JCA. Serum concentrations of hyaluronan and proteoglycan thus differ between disease groups and may reflect different aspects of the arthritic process.
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PMID:Serum concentrations of hyaluronan and proteoglycan in joint disease. Lack of association. 176 88

Cartilage proteoglycans are large molecules consisting of several sub-regions each of which comprises homologous repeating subunits. Comparisons of murine primed popliteal lymph node responses to human cartilage proteoglycans in BALB and B10 congenic mice showed that the major histocompatibility complex (MHC) influences T cell responsiveness to this antigen. H-2k and H-2d were higher responders than H-2b. Responses were MHC class II-restricted, and human cartilage proteoglycans were cross-reactive with mouse cartilage proteoglycans for a BALB/c T cell line. The proportion of proteoglycan-specific T lymphocytes in BALB/c primed popliteal lymph nodes was about 45% lower in females than males. These results show that in mice both MHC haplotype and sex can determine T lymphocyte responsiveness to cartilage proteoglycans. If the same mechanisms apply in humans they could be important in determining the HLA-DR haplotype associations and the predilection of rheumatoid arthritis for females.
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PMID:Comparative analysis of murine T lymphocyte responses to cartilage proteoglycans. 179 24

The presence of T cells and antibodies reactive with heat-shock proteins (hsps) in the joints of patients with rheumatoid arthritis may indicate a role of hsps in this disease. In the present study we examined whether increased temperature and interleukin 1 (IL 1), both of which are elevated in arthritic joints, induced the expression of two hsp70 genes in bovine chondrocyte cultures. We found that heat shock resulted in increased expression of constitutive and inducible hsp70 mRNA species. IL 1 and phorbol 12-myristate 13-acetate (PMA) also induced an increase in the constitutive hsp70 mRNA species, but without affecting the expression of the inducible hsp70 gene. The increase induced by IL 1 was observed only after 3 h, whereas increases induced by PMA were observed within 1 h. For all treatments, the hsp70 mRNA decreased by 24 h. Heat treatment of chondrocytes did not affect levels of collagenase and caseinase activity in the medium, nor did it alter proteoglycan synthesis by these cells.
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PMID:Interleukin 1 induces the expression of a heat-shock gene in chondrocytes. 185 60

Experimental animal models of arthritis, including type II collagen-induced arthritis, proteoglycan-induced arthritis, adjuvant arthritis, pristane-induced arthritis, and streptococcal cell wall-induced arthritis have contributed to recent advances in the understanding of the immunopathology of arthritis. The dissection of the T-cell populations regulating the autoimmune response is currently the most active area of investigation. Research into the mechanism underlying the association of specific class II major histocompatibility complex antigens with arthritis has focused attention on the interaction of particular V beta T-cell subsets with antigens presented in context of permissive major histocompatibility complex antigens. Several models indicate that both the structure of the major histocompatibility complex antigen and the T-cell receptor may be critical in the development of autoimmunity, while the MIs antigen system appears to regulate the availability of T cells with self-reactivity specificities. Studies on the role of heat-shock proteins in experimental arthritis have prompted research into the role of gamma/delta T cells in joint disease, while the availability of recombinant cytokines has permitted the direct analysis of soluble factors. In addition to providing basic insights into autoimmune disease, animal models continue to provide the means to test novel experimental approaches to the treatment of rheumatoid arthritis.
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PMID:Animal models of rheumatoid arthritis. 190 56

Increased amounts of interleukin-8 (IL-8) were detected in synovial fluids of patients with active rheumatoid arthritis (RA) by radioimmunoassay (RIA). The concentration of IL-8 correlated directly with the number of infiltrating neutrophils in synovial fluids. To elucidate the role of IL-8 in neutrophil accumulation at the site of synovitis, the in vivo effects of intraarticular injection of recombinant IL-8 (rIL-8) on leukocytes infiltration into the joint space and synovium were examined. Following a single injection of rIL-8 into the knee joint space of rabbits, redness of the joint and limp became apparent after 4 h and were associated with the rapid infiltration of neutrophilic leukocytes into the joint space and synovial tissues. These effects were time dependent, first becoming evident at 1 h and reaching a plateau in 4 h, and also dose dependent, with a minimal effect being elicited by 100 ng per joint. Although neutrophils were present in the greatest number at 4 h, subsequently mononuclear cells accumulated and became apparent in considerable number after 8 h. Synovial lining cells became ovoid, pleomorphic, and multilayered at 24 h. IL-8 had no effect on the breakdown of proteoglycan of articular cartilage. Based on these findings, IL-8 released from monocytes and synovial cells may be an important contributor to leukocyte accumulation and inflammatory events in the joints of RA.
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PMID:Elevation of interleukin-8 (IL-8) levels in joint fluids of patients with rheumatoid arthritis and the induction by IL-8 of leukocyte infiltration and synovitis in rabbit joints. 193 67

Cartilage contains a number of matrix macromolecules not present in other connective tissues. In tissue processes in disease and in normal turnover of the matrix these molecules are fragmented and released into surrounding fluids, in the case of joints into the synovial fluid. Immunoassay techniques have been developed to quantify these fragments. It appears that increased levels in synovial fluid (SF) correlate to a process in the joint cartilage. With successful therapy the level returns to normal. Interestingly, in early rheumatoid arthritis, i.e., with no discernible cartilage damage by radiography, a high SF level of one major cartilage component (proteoglycan aggrecan/fragments) is prognostic for future extensive cartilage destruction. There are major differences in the levels of proteoglycan fragments between different disease groups. Thus, patients with acute reactive arthritis have high SF levels, while patients with late rheumatoid arthritis with extensive cartilage destruction not surprisingly have subnormal values. Patients with osteoarthritis, even those with fairly extensive cartilage destruction, have elevated levels of proteoglycans/fragments in their SF, perhaps indicative of a more pronounced reparative phase.
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PMID:Macromolecular markers in joint disease. 202 21

The purpose of the present study was to test if agarose could support the maintenance of normal and arthritic human chondrocytes in culture, and under which experimental conditions they could be successfully grown. Cultures of chondrocytes isolated from articular cartilage from patients with rheumatoid arthritis (RA), juvenile rheumatoid arthritis (JRA), and healthy controls were assessed by light microscopy, alcian blue staining, formazan uptake and incorporation of radiosulfate into the extracellular matrix. The results showed that both normal and arthritic chondrocytes proliferated, and synthesized proteoglycan (PG) in agarose in short term and long term culture. Proliferation and PG synthesis occurred at a slower rate in chondrocytes from adult rheumatic patients than from healthy controls. Supplements to the medium influenced chondrocyte proliferation, PG synthesis and release into the medium. Serum from RA patients stimulated chondrocyte responses more than normal human serum (NHS), and NHS promoted PG synthesis more than fetal calf serum (FCS). Exposure to inflammatory synovial fluid (SF) enhanced PG synthesis of healthy chondrocytes, but suppressed it in arthritic chondrocytes. We conclude that species-specific serum is optimal for chondrocyte cultures, and that disease related culture conditions change the chondrocyte response. As metabolic responses of human chondrocytes are maintained in agarose, this culture system appears as a suitable in vitro tool for further studies of human joint disease.
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PMID:Responses of normal and rheumatic human articular chondrocytes cultured under various experimental conditions in agarose. 206 39

Cartilage breakdown in rheumatoid arthritis results from (a) lytic action by synovial enzymes, and (b) release of synovial catabolin, now believed to be a form of interleukin 1 (IL-1), causing chondrocytes to degrade their matrix. Rheumatoid synovial culture media were tested for their ability to stimulate cartilage degradation (proteoglycan release from bovine nasal cartilage discs) and thymocyte proliferation (3H-thymidine incorporation) in the absence or presence of anti-IL-1. Degradation of living cartilage, stimulated 2-fold by synovial culture media, was inhibited up to 80% by anti-IL-1. Residual breakdown in living cartilage and synovial culture media induced breakdown in dead cultures were of similar magnitude, and both were unaffected by antibody treatment. Proteoglycan products released from synovial culture media treated cartilage were of smaller average molecular weight (Sepharose CL-2B), and such size reduction was inhibited by anti-IL-1 treatment. Synovial culture media that stimulated cartilage degradation also stimulated thymocyte proliferation; the latter was fully suppressible by anti-IL-1. One of 8 synovial culture media contained an inhibitor(s) of thymocyte proliferation, removable by dialysis. We conclude (1) rheumatoid synovial catabolin activity is due to a form of IL-1. (2) A minor nonsuppressible component of synovial culture media stimulated breakdown, identical in living and killed cartilage, is due to passive transfer of enzymic activity. (3) Cultured rheumatoid synovium releases both IL-1 and an inhibitor(s) of IL-1 action.
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PMID:Antibody to interleukin 1 inhibits the cartilage degradative and thymocyte proliferative actions of rheumatoid synovial culture medium. 208 32

In a coculture with porcine articular cartilage explants unstimulated blood mononuclear cells (BMC) from patients with rheumatoid arthritis (RA), but not from healthy controls, induced proteoglycan depletion of dead cartilage. Specific stimulation of the RA BMC with Mycobacterium tuberculosis (MT), in comparison with concanavalin A (Con-A), strongly enhanced the proteoglycan depletion of living cartilage; this was not found with the BMC of healthy controls. However, the MT induced proliferative responses of the same BMC were similar in healthy controls and patients with RA. Neither the proliferative response nor the proteoglycan depletion was influenced by the presence of HLA-DR4 in the donor, whether patients with RA or healthy control. The proliferative responses of the RA BMC seemed to correlate inversely with the proteoglycan depletion. We conclude that stimulation of RA BMC with mycobacterial antigens may elicit effector pathways that induce proteoglycan depletion, independent of T cell proliferation.
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PMID:Mycobacterial antigens stimulate rheumatoid mononuclear cells to cartilage proteoglycan depletion. 211 99

Elastase from phagocytes are neutral proteolytic enzymes and potent destructors of elastic fibres, proteoglycan and collagen. Using soluble 3H-elastin as substrate in a cell culture assay we examined the ability of live, adherent human blood neutrophils and monocytes to release elastolytic activity following immune complex (IC) stimulation. While monocytes increased their elastolysis 2 1/2 times in response to IC (p less than 0.01), neutrophils did not but released lactoferrin and produced superoxide. Both cell types could be stimulated by phorbol myristate acetate (PMA) to increase elastolysis (p less than 0.02) and produce superoxide. Thus, when in contact with the elastin substrate, the in vitro response of monocytes and neutrophils to IC differed with respect to elastolytic release. These findings might be of interest in the understanding of cartilage destruction in immunocomplex-mediated diseases such as rheumatoid arthritis.
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PMID:Release of elastolytic activity from human monocytes and granulocytes in vitro by immune complex stimulation. 215 59


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