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)

Rubella and influenza A (H3N2) haemagglutination inhibition (HI) antibody titres and measles complement-fixing (CF), haemagglutination inhibition (HI), haemolysis inhibition (HLI), and ribonucleoprotein gel precipitation (RNP-GP) antibody titres were studied in the serum and synovial fluid of twenty patients with rheumatoid arthritis (RA), two patients with ankylosing spondylitis, and two patients with Reiter's syndrome. Antibody titres were also studied in the serum and CSF of four patients with systemic lupus erythematosus (SLE), one patient with dermatomyositis, and in the synovial fluid only of five patients with osteoarthritic knee effusions. Antibodies were found with each serological technique used in the synovial fluid of RA patients and the antibody titres were usually at about the same level as in the serum. The mean measles (HI, HLI, and RNP-GP) antibody titres were 4 to 6 times higher in the synovial fluid of RA patients than in synovial fluid of patients with osteoarthritic knee effusions, but a corresponding difference was not found in rubella and influenza A antibody titres. The mean measles antibody titres (CF, HI, HKI, and RNP-GP) were consistently higher in the synovial fluid of RA patients without rheumatoid factor than in the synovial fluid of RA patients with rheumatoid factor. In serum this difference was observed only with measles CF titres. The mean measles, antibody titres were consistently lower in the serum and synovial fluid of the RA patients without the synovial fluid haemolytic complement than in the RA patients with this haemolytic complement. No similar differences were found in the rubella and influenza antibody titres. No significant measles antibody titres were found in the CSF of patients with SLE or dermatomyositis.
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PMID:Virus antibodies in serum and synovial fluid of patients with rheumatoid arthritis and other connective tissue diseases. 112 54

Synovial fibroblasts are likely to be a significant source of granulocyte-macrophage colony-stimulating factor (GM-CSF) and granulocyte-CSF (G-CSF), which could be crucial to the pathogenesis of rheumatoid arthritis. Using specific enzyme-linked immunosorbent assays (ELISAs) and Northern analysis, GM-CSF and G-CSF expression were followed in human synovial fibroblast-like cells in response to a number of agents, either alone or in the presence of an optimal stimulatory concentration of interleukin-1 (IL-1). For both CSFs, interferon-gamma (100 U/mL) did not increase their levels but dramatically suppressed the stimulatory action of IL-1, while basic fibroblast growth factor (10(-8) mol/L), although nonstimulatory by itself, potentiated IL-1 action. The glucocorticoid, dexamethasone (10(-7) mol/L), inhibited IL-1-stimulated CSF production. However, evidence was obtained for noncoordinated CSF regulation. Cyclooxygenase inhibitors potentiated the action of IL-1 on GM-CSF synthesis but suppressed G-CSF synthesis, suggesting that endogenous cyclooxygenase products can have opposite effects in modulating the levels of each CSF. Also, the lymphokine, IL-4 (250 pmol/L), slightly inhibited GM-CSF formation in the presence of IL-1 but elevated the G-CSF levels in these cultures without having an effect by itself. Transforming growth factor beta (less than or equal to 20 ng/mL) did not modulate levels of either CSF. Mesenchymal cell production of both GM-CSF and G-CSF is generally viewed as being under coordinate control; our findings suggest that their synthesis in IL-1-stimulated human synoviocytes can be modulated by a number of agents, in some cases with divergent actions depending on which CSF is examined.
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PMID:Cytokine regulation of colony-stimulating factor (CSF) production in cultured human synovial fibroblasts. II. Similarities and differences in the control of interleukin-1 induction of granulocyte-macrophage CSF and granulocyte-CSF production. 137 87

We analyzed expression of HLA-DR and CD14 molecules on myelomonocytic cells and its regulation by various inflammatory cytokines in 6 patients with rheumatoid arthritis (RA) and 4 healthy individuals who had undergone bone marrow aspiration. At start of the bone marrow culture there was a significantly higher number of HLA-DR and CD14 positive bone marrow mononuclear cells in patients with RA than in normals. In addition, RA bone marrow mononuclear cells expressed an up to 10-fold higher mean density of both molecules than normal bone marrow mononuclear cells during the whole culture period of up to 14 days. The effect of the cytokines interferon-gamma (IFN-gamma), tumor necrosis factor alpha (TNF alpha), granulocyte monocyte colony stimulating factor (GM-CSF) and interleukin 1 (IL-1) on the expression of CD14 or HLA-DR was different: IFN-gamma strongly upregulated HLA-DR expression and down-regulated CD14 expression while TNF alpha, GM-CSF and IL-1 mainly stimulated CD14 expression on bone marrow mononuclear cells. Our data suggest that RA bone marrow mononuclear cells exhibit an activated phenotype and that TNF-alpha GM-CSF and IL-1 mainly stimulate the differentiation of bone marrow macrophages whereas IFN-gamma activates them.
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PMID:Activation and differentiation of myelomonocytic cells in rheumatoid arthritis and healthy individuals--evidence for antagonistic in vitro regulation by interferon-gamma and tumor necrosis factor alpha, granulocyte monocyte colony stimulating factor and interleukin 1. 138 Sep 87

Various cytokines were recently found to be involved in the pathogenesis of rheumatoid arthritis (RA) and particularly, cytokines with hematopoietic activity have been detected in synovial tissues. We counted the number of myeloid precursors in terms of granulocyte/macrophage colony forming units (CFU-GM) and the number of stromal cell progenitors in terms of fibroblast colony forming units (CFU-F) in the tibial bone marrow adjacent to the joints affected by RA (n = 21), osteoarthritis (OA) (n = 10), and trauma (n = 2) using the colony formation unit assay. We also quantitated the amounts of interleukin 1 beta (IL-1 beta), IL-6, and granulocyte/macrophage colony stimulating factor (GM-CSF) in the culture supernatant of synovial tissue explants of these patients by enzyme linked immunosorbent assay (ELISA). The mean number (+/- SEM) of CFU-GM in patients with RA (7.4 +/- 4.9) was greater than that in patients with OA (0.5 +/- 0.2), while CFU-GM was not detected in trauma patients. The number of CFU-GM in the tibial bone marrow of patients with RA correlated well with the amount of IL-1 beta (r = 0.64, p < 0.01), but not with GM-CSF or with IL-6 from synovial tissues. These findings suggest that active bone marrow is present adjacent to the affected joints in patients with RA and that hematopoietic activity is influenced by IL-1 beta produced in nearby synovial tissues.
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PMID:Detection of myeloid precursors (granulocyte/macrophage colony forming units) in the bone marrow adjacent to rheumatoid arthritis joints. 146 60

Synoviocytes have been shown to be effector cells capable of synthesizing and secreting a variety of cytokines and growth factors. We demonstrate here that synoviocyte derived conditioned medium has immunoregulatory properties as it enhances human peripheral blood lymphocyte survival in a dose dependent manner in vitro. The effect elicited by synoviocyte derived conditioned medium from patients with rheumatoid arthritis (RA) was greater than that induced by synoviocyte derived conditioned medium from patients with osteoarthritis. Granulocyte-macrophage colony stimulating factor (GM-CSF) was found in synoviocyte derived conditioned medium with significantly higher levels present in synoviocyte derived conditioned medium from patients with RA. Recombinant human GM-CSF induced survival of human lymphocytes in vitro and a monoclonal antibody to human GM-CSF fully abrogated synoviocyte derived conditioned medium induced survival. Our results demonstrate that synoviocyte derived GM-CSF may be important in the retention of lymphocytes, which is a central pathological characteristic of the rheumatoid joint.
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PMID:Synoviocyte derived granulocyte macrophage colony stimulating factor mediates the survival of human lymphocytes. 151 59

Peripheral granulocytes from rheumatoid arthritis and reactive arthritis patients were recently found to express higher levels of a newly defined Ag, termed M6, in comparison to granulocytes from healthy subjects. We present here the molecular characterization of M6 Ag and show that it is a novel human leukocyte activation-associated cell surface glycoprotein. Peripheral lymphocytes do not significantly express M6 Ag, however, it appears upon 3-day PHA-activated T blasts. On monocytes, which constitutively express M6 Ag, it is down-regulated on day 1 but re-induced on day 3 of granulocyte-macrophage CSF stimulation. SDS-PAGE analysis of M6 immunoprecipitates shows a single band of 54 kDa under nonreducing conditions that shifts to 65 kDa under reducing conditions. Endoglycosidase F treatment of M6 immunoprecipitate reveals that 50% of the M6 molecule is composed of N-linked carbohydrates. By modifying the COS cell cloning strategy, we have isolated cDNA clones encoding M6 Ag. M6 cDNA hybridizes with a single mRNA transcript of approximately 1.7 kb in Northern blotting. Comparison analysis of the M6 sequence indicates that M6 Ag is a member of the Ig superfamily and the species homologue of rat OX-47 Ag, mouse basigin (gp42), and chicken HT7 molecule. The highly conserved remarkable transmembrane domain suggests that the M6 Ag may be a component of a multichain complex in the plasma membrane.
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PMID:Human leukocyte activation antigen M6, a member of the Ig superfamily, is the species homologue of rat OX-47, mouse basigin, and chicken HT7 molecule. 163 73

Joint synovium of patients with rheumatoid arthritis plays an important role in initiation and progress of joint diseases. Proliferation and activation of synovial cells, including macrophages, are modulated by various cytokines and arachidoic acid metabolites. Two kinds of cytokines; granulocyte/macrophage colony-stimulating factors (GM-CSF), and monocyte/macrophage colony-stimulating factor (M-CSF) induce the proliferation or activation of monocyte/macrophages, and their progenitor cells or other stromal cells in bone marrow. We investigated the effects of GM-CSF and M-CSF on synovial cells. GM-CSF stimulated the proliferation of synovial cells and its effect was enhanced by the presence of indomethacin, like that of a potent stimulator of synovial cells, interleukin-1 beta (IL-1 beta). But GM-CSF did not induce the production of IL-1 beta. M-CSF neither stimulated the proliferation of synovial cells nor induced production of IL-1 beta by synovial cells. It was suggested that GM-CSF played some role in the proliferation of synovial cells of the joints.
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PMID:Effects of colony-stimulating factors on proliferation and activation of synovial cells. 179 Jun 36

Cytokines and growth factors are important mediators of inflammation and play a major role in both the physiological regulation of bone and cartilage metabolism, and in the destruction of joint-related structures. These complex biological regulatory events have to be regarded as net effects which are dependent on the individual actions of the different cytokines and their corresponding inhibitors in the pericellular environment of the cells present in the inflamed tissues. These effects can be antagonized on various levels by natural or artificial inhibitory molecules. The determination and characterization of cytokines and their inhibitors in body fluids and tissues may contribute to a better understanding of the basic mechanisms of the pathogenesis of inflammatory joint diseases, and may help to develop better modalities of therapy. The objective of the present review is to outline important actions of selected cytokines and growth factors on cells and the surrounding matrix of bone and cartilage in rheumatoid arthritis. It will focus on interleukin-1 (IL-1), IL-1 inhibitors, Tumor-Necrosis-Factor-alpha (TNF-alpha), TNF inhibitors, Interleukin-6 (IL-6), colony-stimulating factors (CSF's), Interferon-gamma (IFN-gamma), growth factors, eicosanoids and prostaglandins, all of which are important in the effector phase of tissue destruction.
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PMID:[The role of cytokines and growth factors in rheumatoid joint destruction]. 179 55

Monocyte recruitment and accumulation in the synovial tissue is pivotal in the evolution of rheumatoid arthritis (RA). In the present study we examined the chemotactic potential of monocytes obtained from synovial fluid (SF) of patients with RA. Functionally, SF monocytes exhibited greatly diminished chemotactic activity to C5a compared with monocytes from the peripheral blood. In contrast, their chemotactic responsiveness to the synthetic peptide, FMLP, was nearly normal. To define a mechanism for this differential chemotactic dysfunction, cell-surface receptors for C5a (C5aR) and FMLP (FMLP-R) were evaluated. Whereas FMLP-R expression was similar on both blood and inflammatory monocytes, C5aR expression was markedly reduced on SF cells. Because decreased C5a binding in certain RA SF samples could not be attributed to free C5a, known or suspected components of inflammatory SF were evaluated for their ability to modulate chemotactic ligand receptors. Bacterial products including LPS and streptococcal cell walls, which are potent monocyte activators, down-regulated C5aR without affecting FMLP-R. Moreover, the cytokines IFN-gamma and granulocyte-macrophage-CSF selectively decreased C5aR in parallel with decreased in vitro chemotactic activity to C5a. Thus, these data indicate that 1) synovial effusions may contain C5a and/or inflammatory mediators that modulate phenotypic and functional changes in monocytes, 2) chemotactic ligand receptors are independently regulated in inflammatory lesions, and 3) decreased C5aR expression and chemotactic potential likely provide a mechanism whereby monocyte-macrophages persist within the inflamed synovium.
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PMID:Modulation of monocyte chemotactic function in inflammatory lesions. Role of inflammatory mediators. 189 61

The effects of GM-CSF, IL-2, IFN-gamma, TNF-alpha and IL-6 on the production of IL-1 (both secreted and cell associated) and TNF-alpha by peripheral blood monocytes were studied. Monocytes were cultured for 20 h in suspension and in serum-free conditions which minimized background stimulation of monokine production. GM-CSF, IL-2 and TNF-alpha directly induced the production of cell-associated IL-1 but little or no IL-1 or TNF-alpha secretion. Combination of GM-CSF with IFN-gamma, IL-2 or TNF-alpha synergistically enhanced IL-1 secretion and had an additive effect on cell-associated IL-1 production. Combination of IL-2 with IFN-gamma or TNF-alpha also synergistically enhanced IL-1 secretion but the effect on cell-associated IL-1 production was less than additive. GM-CSF synergistically enhanced TNF-alpha secretion induced by IFN-gamma but not by lipopolysaccharide. GM-CSF did not enhance TNF-alpha secretion induced by IL-2 or TNF-alpha. In contrast, IL-2 synergistically enhanced TNF-alpha secretion induced by IFN-gamma. These results are discussed in relation to cytokine involvement in rheumatoid arthritis.
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PMID:Effects of granulocyte-macrophage colony-stimulating factor (GM-CSF), IL-2, interferon-gamma (IFN-gamma), tumour necrosis factor-alpha (TNF-alpha) and IL-6 on the production of immunoreactive IL-1 and TNF-alpha by human monocytes. 190 83


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