Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:3.4.24.3 (collagenase)
18,340 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

A patient with chronic Lyme arthritis and roentgenographic evidence of bony erosion underwent a synovectomy; proliferative synovium (pannus), containing aggregates of small lymphocytes, was found adherent to eroded cartilage and bone. During 8 days in tissue culture, the synovial cells produced large amounts of collagenase and prostaglandin E2, but only low levels of both neutral and acid proteinases. Sixty-seven percent of the lymphocytes from the synovium were T cells; 19% were B cells. Attempts to identify agent/antigen in the synovial cells were unsuccessful. Thus, the synovium of this patient, whose disease appears to be tick-transmitted, resembles that of rheumatoid arthritis. This finding further supports the hypothesis that many possible agents, including infectious ones, trigger a common pathway in synovium, which leads to joint destruction.
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PMID:Elevated levels of collagenase and prostaglandin E2 from synovium associated with erosion of cartilage and bone in a patient with chronic Lyme arthritis. 624 4

The cause of persistent arthritis in patients with Lyme disease who have received standard antibiotic therapy remains an area of debate. In this study, synovial fluid levels of matrix metalloproteinases (MMPs) were compared in persons with untreated and antibiotic-resistant Lyme arthritis. Levels of MMP-1 and MMP-3, as determined by ELISA, were higher in untreated patients (P=.0064 and P=.002, respectively), whereas levels of MMP-8 and MMP-9 were higher in antibiotic-resistant patients (P=.0002 and P=.0014, respectively). In vitro studies of chondrocyte cultures infected with Borrelia burgdorferi revealed induction of MMP-1 and MMP-3 but not of MMP-8 or MMP-9. Neither Staphylococcus aureus nor lipopolysaccharide stimulated MMP-1 or MMP-3 release from these cells. The mechanism of recognition of B. burgdorferi may be through CD14 and toll-like receptor-2, which were up-regulated in the presence of B. burgdorferi. These findings suggest different stimuli for MMP induction in untreated and antibiotic-resistant Lyme arthritis.
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PMID:Differences in synovial fluid levels of matrix metalloproteinases suggest separate mechanisms of pathogenesis in Lyme arthritis before and after antibiotic treatment. 1142 14

Matrix metalloproteinases (MMPs) are induced from host tissues in response to Borrelia burgdorferi. Upregulation of MMPs may play a role in the dissemination of the organism through extracellular matrix tissues, but it can also result in destructive pathology. Although mice are a well-accepted model for Lyme arthritis, there are significant differences compared to human disease. We sought to determine whether MMP expression could account for some of these differences. MMP expression patterns following B. burgdorferi infection were analyzed in primary human chondrocytes, synovial fluid samples from patients with Lyme arthritis, and cartilage tissue from Lyme arthritis-susceptible and -resistant mice by using a gene array, real-time PCR, an enzyme-linked immunosorbent assay, and immunohistochemistry. B. burgdorferi infection significantly induced transcription of MMP-1, -3, -13, and -19 from primary human chondrocyte cells. Transcription of MMP-10 and tissue inhibitor of metalloprotease 1 was increased with B. burgdorferi infection, but protein expression was only minimally increased. The synovial fluid levels of MMPs from patients with high and low spirochete burdens were consistent with results seen in the in vitro studies. B. burgdorferi-susceptible C3H/HeN mice infected with B. burgdorferi showed induction of MMP-3 and MMP-19 but no other MMP or tissue inhibitor of metalloprotease. As determined by immunohistochemistry, MMP-3 expression was increased only in chondrocytes near the articular surface. The levels of MMPs were significantly lower in the more Lyme arthritis-resistant BALB/c and C57BL/6 mice. Differences between human and murine Lyme arthritis may be related to the lack of induction of collagenases, such MMP-1 and MMP-13, in mouse joints.
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PMID:Induction of host matrix metalloproteinases by Borrelia burgdorferi differs in human and murine lyme arthritis. 1561 47