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Query: UMLS:C0003864 (arthritis)
 69,039 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Endothelial cells play a fundamental role in the pathogenesis of chronic inflammatory arthritis in humans such as rheumatoid arthritis (RA), as well as experimental animal models such as streptococcal cell wall (SCW) arthritis in Lewis (LEW/N) rats. This review summarizes data in support of this concept. The earliest apparent abnormalities in synovial tissues of patients with RA and Lewis rats with SCW arthritis appear to reflect microvascular endothelial cell activation or injury. At the molecular level, the abnormalities include enhanced expression by endothelial cells of activation markers such as class II major histocompatibility complex antigens, phosphotyrosine, leukocyte adhesion molecules, oncoproteins such as c-Fos and c-Myc, and metalloproteinases such as collagenase and transin/stromelysin. The development of severe, chronic, destructive arthritis is dependent upon thymic-derived lymphocytes and is accompanied by tumorlike proliferation of cells in the synovial connective tissue stroma (blood vessels and fibroblastlike cells), which results in resorptive destruction of bone and cartilage. Multiple criteria support the analogy to a neoplastic process. Paracrine and autocrine factors such as interleukin-1 (IL-1), platelet-derived growth factor (PDGF), transforming growth factor-beta (TGF-beta), and heparin-binding fibroblast growth factors (HBGF, FGF) appear to play important roles in the generation of these lesions. Finally, in addition to the autocrine and paracrine regulatory factors, neuroendocrine factors, particularly the hypothalamic-pituitary-adrenal axis, appear to be involved in the counterregulation of the inflammatory process. The counterregulatory effects are mediated, in part, by inhibition of endothelial cell activation by corticosteroids.
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PMID:Endothelial cells and the pathogenesis of rheumatoid arthritis in humans and streptococcal cell wall arthritis in Lewis rats. 205 44

The amount of active neutrophil (PMN) collagenase released extracellularly is dependent on the PMN-activating ligand. Neutrophils stimulated with soluble ligands, including FMLP, platelet-activating factor, or heat-aggregated IgG, released very little active collagenase, in contrast to cells stimulated with opsonized zymosan or surface-bound IgG. However, opsonized zymosan and surface-bound IgG did not differ appreciably from soluble ligands in effecting PMN production of superoxide, release of the specific granule component lactoferrin, or total (latent plus active) collagenase release, which suggests that there is more efficient collagenase activation during PMN stimulation with surface-bound ligands. These results suggest a role for surface (cartilage)-bound IgG in the release and activation of human neutrophil collagenase in the joints of patients with rheumatoid arthritis.
Arthritis Rheum 1990 Feb
PMID:Ligand-dependent release of active neutrophil collagenase. 215 97

Articular cartilage from arthritic joints of rats immunized with type II collagen is severely depleted of proteoglycans. Depletion begins within 48 hours after the onset of inflammation, prior to extensive pannus formation, and may represent a critical first step in cartilage destruction. We have immunolocalized stromelysin, an enzyme that is believed to play a major role in the pathologic degradation of proteoglycans, in the joints of rats with collagen-induced arthritis. Immunoperoxidase staining of frozen tissue sections demonstrated the presence of stromelysin in both the synovium and chondrocytes. In contrast, collagenase was localized primarily to the pannus-cartilage junction. Neither enzyme was detectable in joints from normal animals. To test the hypothesis that chondrocytes respond directly to inflammatory mediators by increasing the production of stromelysin, isolated chrondrocytes were incubated with various concentrations of interleukin-1. The culture media were also assayed for the presence of stromelysin by immunoreactivity on Western blots and by analysis of enzymatic activity on casein substrate gels. A 3-fold increase in a doublet of proteins synthesized in response to 10 units/ml of interleukin-1 was observed. These proteins also immunoreacted with the stromelysin antibody and degraded casein. Northern blotting results established that the increased levels of stromelysin were accompanied by increases in stromelysin-specific messenger RNA levels. These results suggest that stromelysin is responsible for proteoglycan degradation in early inflammatory arthritis, and that chondrocytes may play a direct role in the earliest stages of the degradation of their own matrices.
Arthritis Rheum 1990 Mar
PMID:The role of stromelysin in the cartilage destruction that accompanies inflammatory arthritis. 215 11

The reported prevalence of interstitial lung disease in patients with rheumatoid arthritis has varied from 10% to 50%, yet less than 5% of patients with arthritis develop severe fibrosing interstitial lung disease. This suggests that subclinical disease may not always presage progressive disease. Bronchoalveolar lavage fluid from patients with rheumatoid arthritis and either clinically evident interstitial lung disease or subclinical disease was examined for the presence of factors with a putative role in the development of interstitial fibrosis. Patients with subclinical disease were identified by prospective radiographic and lung function screening of 93 patients with rheumatoid arthritis. Fourteen patients were identified in this manner and an association between subclinical disease and smoking history was noted. Eleven patients with established interstitial lung disease had increased neutrophils (p less than 0.05), collagenase, and type III procollagen N terminal peptide levels (p less than 0.01) in the bronchoalveolar lavage fluid. Preliminary characterisation of the bronchoalveolar lavage collagenase suggested that it originated from neutrophils. Ten patients with subclinical interstitial lung disease underwent bronchoalveolar lavage. Of these, one had increased neutrophils and two had increased collagenase concentrations--abnormalities associated with advanced interstitial lung disease and a poor prognosis. These results suggest that in arthritis patients with evidence of subclinical pulmonary interstitial disease bronchoalveolar lavage might be useful in identifying those who may require careful monitoring in the hope that early treatment will prevent severe fibrosis.
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PMID:Bronchoalveolar lavage in patients with mild and severe rheumatoid lung disease. 216 54

In order to determine whether interleukin 6 (IL-6) is involved in the pathogenesis of the cartilage destruction observed in arthritis, the effect of human recombinant IL-6 on collagenase production and proteoglycan synthesis by bovine articular chondrocytes was examined. Addition of IL-6 (1.0 to 1000 U/ml) to the culture medium did not stimulate collagenase production or alter proteoglycan secretion. Whereas human purified interleukin 1 (IL-1) (20 U/ml) stimulated collagenase production and inhibited proteoglycan synthesis. Furthermore addition of IL-1 (20 U/ml) to chondrocyte cultures did not stimulate the chondrocytes to produce IL-6. Under our experimental conditions, IL-6 did not stimulate chondrocytes to proliferate as measured by [3H] thymidine incorporation. This would suggest that IL-6 is not involved in mediating cartilage loss.
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PMID:Comparison of the effect of interleukin 6 and interleukin 1 on collagenase and proteoglycan production by chondrocytes. 217 Jun 44

Levels of tissue inhibitor of metalloproteases (TIMP) and plasminogen activator (PA)/plasmin were measured and the distribution of PA was studied by immunohistochemical techniques in cartilage and synovium samples from dogs subjected to sectioning of the anterior cruciate ligament of their right knees and sham operation of their left knees (controls). Twenty-three animals were divided into 3 groups and killed at 2, 4, or 8 weeks after surgery. The levels of PA and plasmin were found to be significantly elevated in the osteoarthritic (OA) knee cartilage and synovium at all times after surgery, except for levels of PA in the OA cartilage at 2 weeks. There was a positive correlation between the levels of PA and plasmin in the synovial membrane (r = 0.64, P less than 0.001). In OA knees, the presence of high levels of total and active collagenase was detected in cartilage and in synovium. The levels of these 2 forms of collagenase showed a positive correlation both in cartilage (r = 0.65, P less than 0.001) and in synovium (r = 0.77, P less than 0.001). The levels of TIMP in cartilage from OA and sham operated knees were similar. Although the TIMP level was increased in the OA synovium, it was found only in trace amounts in cartilage. Immunohistochemical studies revealed that both forms of PA, urokinase-type PA and tissue-type PA, and TIMP were present in OA tissues. In the synovium, they were found mainly in monocyte/macrophages, synovial lining cells, and blood vessel cells. In OA cartilage, PA was present only at the superficial level in chondrocytes and in cartilage matrix, whereas TIMP was present in chondrocyte lacunae throughout the full thickness of the cartilage. TIMP was also detected in the superficial level of cartilage from sham operated knees. The results of this study indicate that in OA tissues, there are conditions that favor the synthesis and activation of metalloproteases. PA and plasmin are likely to play an important role in the physiologic activation of metalloproteases, although they are probably not the only system involved in this process. The lack of increased TIMP levels in the OA cartilage, in the presence of increased metalloprotease activity, is also a possible contributing factor in the enzymatic degradation of this tissue.
Arthritis Rheum 1990 Oct
PMID:Imbalance between the mechanisms of activation and inhibition of metalloproteases in the early lesions of experimental osteoarthritis. 217 38

The effects of binary combinations of the recombinant human cytokines, interleukin-1 beta (rHuIL-1 beta), tumor necrosis factor alpha (rHuTNF alpha), and gamma-interferon (rHu gamma-IFN) on the production of prostaglandin E (PGE), hyaluronic acid (HA), and collagenase by human synovial fibroblasts in culture were investigated. All 3 were stimulated by rHuIL-1 beta and rHuTNF alpha alone, but not by rHu gamma-IFN. Stimulation with rHuIL-1 beta and rHuTNF alpha occurred at femtomolar and picomolar concentrations, respectively, and maximal stimulation by rHuIL-1 beta was several times greater than that by rHuTNF alpha. Stimulation of PGE and collagenase production with rHuIL-1 beta or rHuTNF alpha was depressed by rHu gamma-IFN, depending on the concentration used. In contrast, stimulation of HA production with rHuIL-1 beta or rHuTNF alpha was unaffected or increased somewhat with rHu gamma-IFN. Combinations of rHuIL-1 beta or rHuTNF alpha had marked synergistic effects on PGE and collagenase production. However, when rHuIL-1 beta effects were maximal, rHuTNF alpha had an additive effect. These cytokines had only additive effects on HA production, however, and when rHuIL-1 beta effects were maximal, rHuTNF alpha produced no further stimulation. These data suggest that the secretory activities of synovial fibroblasts can be influenced by a combination of cytokines and is dependent on the type of cytokine present and its concentration.
Arthritis Rheum 1990 Oct
PMID:Synergistic, additive, and antagonistic effects of interleukin-1 beta, tumor necrosis factor alpha, and gamma-interferon on prostaglandin E, hyaluronic acid, and collagenase production by cultured synovial fibroblasts. 217 39

The production of collagenase by human articular chondrocytes in response to interleukin-1 beta is inhibited in a dose-dependent manner by interferon-gamma (1-1,000 units/ml). The analysis of culture medium samples by Western blotting and the measurement of levels of tissue inhibitor of metalloproteinases suggest that the decrease in measurable collagenase activity is primarily due to the inhibition of procollagenase production. These results provide evidence of a role for interferon-gamma in limiting connective tissue degradation.
Arthritis Rheum 1990 Nov
PMID:Inhibition of interleukin-1-induced collagenase production in human articular chondrocytes in vitro by recombinant human interferon-gamma. 217 7

Interleukin-1 (IL-1) has been shown to regulate glycosaminoglycan (GAG) synthesis. We therefore investigated whether an IL-1 inhibitor or IL-6 modulates IL-1 biologic activities in human synovial cells and cultured articular cartilage. We found that in the presence of a constant amount of IL-1 beta, stimulation of hyaluronic acid (HA) synthesis by the IL-1 inhibitor was inhibited in a dose-dependent manner. Similarly, the decrease in sulfated GAG synthesis induced by IL-1 was reversed by the addition of the IL-1 inhibitor. In contrast, IL-6 did not affect the production of HA, prostaglandin E2, or collagenase in synovial cells, nor did it affect GAG in organ cultures when tested in the presence or absence of IL-1 beta. Hence, IL-6 was ineffective in modulating IL-1 bioactivities on HA or sulfated GAG synthesis. These results emphasize the importance of IL-1 and IL-1 inhibitor in connective tissue destruction and raise questions concerning the role of IL-6 in this pathogenesis.
Arthritis Rheum 1990 Dec
PMID:Modulation of the effects of interleukin-1 on glycosaminoglycan synthesis by the urine-derived interleukin-1 inhibitor, but not by interleukin-6. 217 10

The activity of stromelysin and collagenase was determined in fibrillated human OA cartilage using labeled proteoglycans and type II collagen as substrates. In vitro paracetamol had no effect on metalloprotease whereas TA induced a significant inhibition of stromelysin. In cartilage and synovium from nine patients treated with TA and nine patients treated with paracetamol during 8 weeks before surgery for hip OA, stromelysin activity was significantly lower in the TA than in the paracetamol group. The results suggest that TA has a potential chondroprotective effect in OA.
Semin Arthritis Rheum 1990 Feb
PMID:Cartilage degradative enzymes in human osteoarthritis: effect of a nonsteroidal antiinflammatory drug administered orally. 231 5


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