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

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.
 ...
PMID:Ligand-dependent release of active neutrophil collagenase. 215 97

Collagenase has been implicated as playing an important role in the connective tissue destruction that is a major feature of rheumatoid arthritis. Numerous cell types in the hyperplastic rheumatoid synovium are capable of synthesizing collagenase. Past studies have used predominantly synovial fibroblasts in culture as a model system for the regulation of collagenase production, but the major cellular source of the enzyme in vivo has not been determined. Using the techniques of in situ hybridization histochemistry and indirect immunofluorescence, we determined the cellular source of collagenase in frozen sections of human synovium. Collagenase mRNA production was localized to cells along the synovial lining layer in rheumatoid arthritis. These were identified as the macrophage-like Type A synovial lining cells by immunofluorescence with antibody LeuM3. Endothelial cells, fibroblasts, and T and B lymphocytes were devoid of detectable collagenase mRNA. Synovial tissue sections from patients with osteoarthritis and trauma did not contain detectable collagenase mRNA. These data identify the Type A macrophage-like synovial lining cell as the primary source of collagenase mRNA in vivo in the rheumatoid arthritis synovium and, potentially, as a major effector cell in the tissue destruction of the disease.
 ...
PMID:Localization of collagenase mRNA in rheumatoid arthritis synovium by in situ hybridization histochemistry. 215 14

Deposits of IgG localized to collagen bundles/extracellular matrix components occurred in skin biopsies from patients with primary fibromyalgia (PF). None of these patients demonstrated a positive lupus band test. Control skin biopsies from healthy controls were negative but showed intense reactivity for IgG after collagenase treatment. PF-skin attached both homologous and heterologous serum IgG in indirect immunofluorescence, which may point to a qualitative alteration of dermal matrix components in PF. Skin from patients with systemic lupus erythematosus and rheumatoid arthritis showed a lower dermal fluorescence intensity than in PF patients. The cause of the presence of IgG in dermal tissue from PF patients is unclear. It may be caused by a non-specific attachment of IgG to the extracellular matrix related, for example, to tissue hypoxia and/or increased capillary leakage due to an increased number of mast cells in the PF-skin.
 ...
PMID:Attachment of IgG to dermal extracellular matrix in patients with fibromyalgia. 215 58

The effects of recombinant interferon gamma (rIFN gamma) on the in vitro growth of adherent synovial fibroblast-like cells from patients with rheumatoid arthritis (RA) and also on the release of prostaglandin E2 and collagenase from these cells stimulated with recombinant interleukin-1 beta (rIL-1 beta) were investigated. The growth of adherent synovial cells from six of nine samples, determined by [3H]thymidine incorporation, was inhibited by rIFN gamma in a manner dependent on dose. The release of prostaglandin E2 and collagenase from adherent synovial cells stimulated with rIL-1 beta was also suppressed by rIFN gamma in all samples tested, though the basal release of these inflammatory mediators was little influenced. No apparent correlation between inhibition of proliferation by rIFN gamma and either inhibition by rIFN gamma of rIL-1 beta stimulated prostaglandin E2 release or the endogenous synthesis of prostaglandins was found.
 ...
PMID:Effects of interferon gamma on cultured synovial cells from patients with rheumatoid arthritis: inhibition of cell growth, prostaglandin E2, and collagenase release. 216 88

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.
 ...
PMID:Bronchoalveolar lavage in patients with mild and severe rheumatoid lung disease. 216 54

Collagenase production by synovial fibroblast-like cells (synoviocytes) plays a major role in cartilage and bone destruction in rheumatoid arthritis. Interleukin-1 (IL-1) increases collagenase secretion by elevating the steady state levels of collagenase mRNA in cultured rheumatoid synoviocytes, while all-trans-retinoic acid (RA) has the opposite effect. We have studied the regulation of collagenase gene transcription by IL-1 and RA in synoviocytes by transient transfection of plasmid constructs containing deletion mutants of the 5'-flanking region of the collagenase gene or the isolated phorbol ester-responsive element ligated to a chloramphenicol acetyltransferase reporter gene. We show that the phorbol ester-responsive element of the collagenase gene mediates both positive and negative regulatory effects, respectively, of IL-1 and RA on transcription. In addition, we show that IL-1 and 12-O-tetradecanoyl-phorbol-13-acetate transiently induce c-jun and c-fos expression and that retinoic acid inhibits IL-1 and 12-O-tetradecanoyl-phorbol-13-acetate induction of c-fos, but not c-jun. These results suggest that RA inhibits collagenase transcription at least in part through inhibition of c-fos.
 ...
PMID:Interleukin-1 stimulates and all-trans-retinoic acid inhibits collagenase gene expression through its 5' activator protein-1-binding site. 217 24

Loss of connective tissue integrity occurs in many disease processes, including rheumatoid arthritis and osteoarthritis. Although there is a high incidence of these diseases in the developed world, there is no treatment that prevents the tissue damage that occurs. Several lines of evidence suggest that uncontrolled connective tissue metalloproteinase activity is responsible for the damage, and as a consequence the inhibition of these enzymes has become the target for therapeutic intervention. Several connective tissue metalloproteinases, including collagenase, stromelysin, and gelatinase, together with tissue inhibitors of metalloproteinases (TIMPs), have been described. Because of difficulties in isolating the metalloproteinases in sufficient quantity as pure separate enzymes, however, very little knowledge has accumulated about their detailed biochemistry. For similar reasons the way in which TIMPs inhibit tissue metalloproteinases is not yet fully understood. In this article it is shown how cloning metalloproteinase and TIMP cDNAs can provide information about the structure of these enzyme and inhibitor families and how the cDNAs can be used to generate recombinant cell lines from which enzymes and inhibitors can be readily purified for further studies.
 ...
PMID:The tissue metalloproteinase family and the inhibitor TIMP: a study using cDNAs and recombinant proteins. 219 98

Tissue inhibitor of metalloproteinases (TIMP) is the major inhibitor of collagenase, gelatinase, proteoglycanase, stromelysin, and metalloelastases. An imbalance between proteases and inhibitors has been implicated in numerous disease processes including tumor invasion, rheumatoid arthritis, emphysema, and aortic aneurysm disease. The purpose of this investigation was to develop a polyclonal antibody to recombinant TIMP and establish an immunoassay to measure immunoreactive protein in normal and diseased tissues. A polyclonal antibody was produced in rabbit against recombinant human TIMP which was characterized and used to establish a radioimmunoassay. The assay was used to measure immunoreactive protein in fibroblast conditioned medium, human serum, and aortic extracts. There was more immunoreactive TIMP in matrix associated urea extracts than soluble salt extracts from human aorta, suggesting that TIMP is matrix associated. The sensitivity of the assay enables the specific measurement of this inhibitor in serum, fibroblast culture medium, and tissue extracts.
 ...
PMID:Tissue inhibitor of metalloproteases (TIMP) is matrix associated in aortic tissue: report of a radioimmunoassay. 232 85

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.
 ...
PMID:Alpha 2-macroglobulin-proteinase complexes as correlated with alpha 1-proteinase inhibitor-elastase complexes in synovial fluids of rheumatoid arthritis patients. 242 37

Auranofin, an orally gold preparation, effective in the treatment of rheumatoid arthritis, was found to be a potent noncytotoxic inhibitor of histamine and collagenase release from mast cells and polymorphonuclear (PMN) leukocytes respectively. Histamine release has been inhibited by auranofin in dose-dependent fashion. Auranofin at concentration of 10(-5) M inhibited 100% of the release, lower concentration 10(-6) M and 10(-7) M produced 80 and 40% decrease. The exposure of PMN-leukocytes to auranofin caused also dose-dependent inhibition of collagenase release. Auranofin at a concentration of 10(-4) M produced a marked reduction (75-100%) of enzyme release from human and rat blood PMN-leukocytes. The modest inhibition 40 and 15-20% at a concentration of 10(-5) M and 10(-6) M respectively was obtained. Auranofin more significantly suppressed collagenase release from leukocytes isolated from inflammatory exudate. Decrease of 100, 80 and 60% were observed upon addition of 10(-4) M, 10(-5) M and 10(-6) M of auranofin. These results suggest that therapeutic action of auranofin may be caused, at least in part, by the inhibition of cellular release of histamine and collagenase in the course of inflammation.
 ...
PMID:Auranofin modulates mast cell histamine and polymorphonuclear leukocyte collagenase release. 242 96


<< Previous 1 2 3 4 5 6 7 8 9 10 Next >>