Immunoassays for the Detection of Human Collagenase, Stromelysin, Tissue Inhibitor of Metallo-proteinases (TIMP) and Enzyme-Inhibitor Complexes

Cooksley, Susan; Hipkiss, Jayne B.; Tickle, Simon; E, Holmes-Ievers; Docherty, Andrew; Murphy, Gillian; Lawson, Alastair D. G.

doi:10.1016/s0934-8832(11)80183-6

Cited by 88 publications

(53 citation statements)

References 22 publications

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“…In contrast, when using MAC 15 instead of MAC 19 TIMP-1/MMP-9 complexes were detected (13.23 and 8.46 milliabsorbance units/min at complex concentrations of 16 and 8 g/liter, respectively, compared with background samples, which generated a signal of 0.1 milliabsorbance unit/min). In support of the specificity of MAC 19 for uncomplexed TIMP-1, Cooksley et al (28) have previously demonstrated that MAC 19 does not recognize other TIMP-1/MMP complexes such as TIMP-1/MMP-1 and TIMP-1/ MMP-3 as well as the closely related molecules TIMP-2, -3, and -4. These results also confirm what has been reported previously (29) that when using MAC 15 as detection antibody the total amount of TIMP-1 is measured as this antibody binds both uncomplexed TIMP-1 and TIMP-1 in complex with MMPs.…”

Section: Resultsmentioning

confidence: 94%

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Measurement of the Uncomplexed Fraction of Tissue Inhibitor of Metalloproteinases-1 in the Prognostic Evaluation of Primary Breast Cancer Patients*

Würtz¹,

Christensen

Schrohl³

et al. 2005

Molecular & Cellular Proteomics

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Several studies have demonstrated an association between high tumor tissue levels of total tissue inhibitor of metalloproteinases-1 (TIMP-1) and a poor prognosis of primary breast cancer patients. In the present study we investigated whether measurements of the uncomplexed fraction of TIMP-1 added prognostic information to that already obtained from total TIMP-1. We measured the uncomplexed fraction of TIMP-1, using a thoroughly validated ELISA specific for this fraction, in 341 tumor tissue extracts obtained from patients with primary breast cancer. These measurements were related to previously performed measurements of total TIMP-1 as well as to patient outcome. The observation time was 8.3 years (range, 7.3-11.3 years). During this period 136 patients died, and 153 patients experienced recurrence of disease. Cox regression analysis of recurrence-free survival (RFS) suggested that a score based on both uncomplexed and total TIMP-1, reflecting the tumor level of TIMP-1/MMP complexes, would be a more precise estimate of prognosis than total TIMP-1 alone. Univariate survival analysis showed a highly significant relationship between high values of the score and poor outcomes for RFS (p ‫؍‬ 0.0002; hazard ratio ‫؍‬ 2.7; 95% confidence interval, 1.5-4.8). Similar results were found for overall survival (p ‫؍‬ 0.0001; hazard ratio ‫؍‬ 3.3; 95% confidence interval, 1.8 -6.3). Multivariate analysis of RFS and overall survival demonstrated that the score was significant including the classical prognostic factors used in breast cancer (p < 0.0001). The present study raises the hypothesis that it is the tumor level of TIMP-1/MMP complexes (i.e. activated matrix metalloproteinases) rather than TIMP-1 itself that determines prognosis, supporting the use of the combined score and not only total TIMP-1 in stratification of breast cancer patients. Molecular & Cellular Proteomics 4:483-491, 2005.

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Section: Resultsmentioning

confidence: 94%

“…The total amount of TIMP-1 was measured using a TIMP-1 ELISA thoroughly validated for tumor tissue extracts (16,35). In this assay TIMP-1 was detected using a murine monoclonal anti-TIMP-1 antibody (MAC 15), which binds uncomplexed TIMP-1 as well as TIMP-1 in complex with MMPs (28,30), thus measuring the total amount of TIMP-1.…”

Section: Methodsmentioning

confidence: 99%

Measurement of the Uncomplexed Fraction of Tissue Inhibitor of Metalloproteinases-1 in the Prognostic Evaluation of Primary Breast Cancer Patients*

Würtz¹,

Christensen

Schrohl³

et al. 2005

Molecular & Cellular Proteomics

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“…Concentrations of MMP-3 and TIMP-1 were determined by sandwich ELISAs, using monoclonal and polyclonal antibodies, raised against the canine recombinant proteins, as described earlier (Cooksley et al 1990, Bayne et al 1992, Lohmander et al 1993. All assays use a monoclonal antibody against the enzyme or inhibitor as a trapping reagent.…”

Section: Assays Of Stromelysin (Mmp-3) and Tissue Inhibitor Of Metallmentioning

confidence: 99%

Elevated levels of synovial fluid PLA₂, strome-lysin (MMP-3) and TIMP in early osteoarthrosis after tibial valgus osteotomy in young beagle dogs

Panula

Lohmander

Rönkkö³

et al. 1998

Acta Orthopaedica Scandinavica

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“…Medium was harvested after each day of treatment of cartilage slices; TIMP-1 and stromelysin were measured by enzyme-linked immunosorbent assay (56,57). The assay system for stromelysin (MMP-3) measures not only proMMP-3, but also the active form of MMP-3, as well as MMP-3 complexed with TIMP-I or TIMP-2.…”

mentioning

confidence: 99%

The superficial layer of human articular cartilage is more susceptible to interleukin‐1–induced damage than the deeper layers

Häuselmann

Flechtenmacher

Michal

et al. 1996

Arthritis & Rheumatism

111

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Objective. To compare the responses of chondrocytes from superficial and deep layers of normal human articular cartilage to interleukin-1 (IL-1) and IL-1 receptor antagonist protein (IRAP), and to evaluate the binding sites for IL-1 on these cells.Methods. Cartilage and chondrocytes from superficial and deeper layers of human femoral condyles were cultured with and without IL-1 in the presence and absence of IRAP. The effect of these agents on %-proteoglycan synthesis and catabolism and production of stromelysin and tissue inhibitor of metalloproteinases 1 (TIMP-1) were measured by biochemical and immunologic assays. Receptor binding was evaluated using '251-labeled IL-1.Results. IL-1 induced more severe inhibition of proteoglycan synthesis and a lower ratio of secreted TIMP-kstromelysin in chondrocytes from superficial cartilage than those from deeper cartilage. IRAP blocked responses to IL-1 more effectively in chondro- Submitted for publication April 10, 1995; accepted in revised form September 22, 1995.cytes from deep cartilage than those from superficial cartilage. Chondrocytes from the articular surface showed approximately twice the number of high-mity binding sites for IL-1 as did cells from deep cartilage.Conclusion. Chondmytes from the surface of articular cartilage show a greater vulnerability to the harmful effects of IL-1 and are less responsive to the potential therapeutic effects of IRAP than cells in the deeper layers of the tissue.Treatment of cartilage tissue in vitro with IL-1 (1,2) or injection of IL-1 into the synovial cavity (3,4) results in inhibition of synthesis of proteoglycans (PGs) (5-9), enhanced production of prostaglandin E2 (PGE,) (10) and metalloproteinases (1 l), and excessive catabolism of PGs. Together these conditions contribute to loss of cartilage matrix and inadequate tissue repair. Based on experimental results and on the finding of IL-1, PG fragments, and proteolytic enzymes in inflamed joints (12)(13)(14), it is widely accepted that IL-1 plays an important role in cartilage erosion in inflammatory joint diseases. Because PG synthesis is usually upregulated during the early stages of osteoarthritis (15), IL-1 has been given little attention as a potential mediator of early metabolic changes in articular cartilage. In patients, on the other hand, especially during the inflammatory episodes which almost always develop at late stages of the disease, IL-1 appears to play a significant role in suppressing the synthesis and repair mechanism (16). IL-1 a and IL-Ip, the 2 agonist isoforms of 1L-1 (17-21), bind to specific cell-membrane receptors and set in motion complex signal transduction pathways which are not yet fully understood (22). The human recombinant form of IL-1 receptor antagonist protein also binds to the same receptors, but since it fails to initiate signal transduction or elicit biological responses, it blocks cellular ARTICULAR SURFACE SUSCEPTIBILITY TO IL-1 479 responses to IL-1 (23) and acts as a pure antagonist (24)(25)(26)(27)(28).Two structurally related c...

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Immunoassays for the Detection of Human Collagenase, Stromelysin, Tissue Inhibitor of Metallo-proteinases (TIMP) and Enzyme-Inhibitor Complexes

Cited by 88 publications

References 22 publications

Measurement of the Uncomplexed Fraction of Tissue Inhibitor of Metalloproteinases-1 in the Prognostic Evaluation of Primary Breast Cancer Patients*

Measurement of the Uncomplexed Fraction of Tissue Inhibitor of Metalloproteinases-1 in the Prognostic Evaluation of Primary Breast Cancer Patients*

Elevated levels of synovial fluid PLA₂, strome-lysin (MMP-3) and TIMP in early osteoarthrosis after tibial valgus osteotomy in young beagle dogs

The superficial layer of human articular cartilage is more susceptible to interleukin‐1–induced damage than the deeper layers

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Immunoassays for the Detection of Human Collagenase, Stromelysin, Tissue Inhibitor of Metallo-proteinases (TIMP) and Enzyme-Inhibitor Complexes

Cited by 88 publications

References 22 publications

Measurement of the Uncomplexed Fraction of Tissue Inhibitor of Metalloproteinases-1 in the Prognostic Evaluation of Primary Breast Cancer Patients*

Measurement of the Uncomplexed Fraction of Tissue Inhibitor of Metalloproteinases-1 in the Prognostic Evaluation of Primary Breast Cancer Patients*

Elevated levels of synovial fluid PLA2, strome-lysin (MMP-3) and TIMP in early osteoarthrosis after tibial valgus osteotomy in young beagle dogs

The superficial layer of human articular cartilage is more susceptible to interleukin‐1–induced damage than the deeper layers

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Elevated levels of synovial fluid PLA₂, strome-lysin (MMP-3) and TIMP in early osteoarthrosis after tibial valgus osteotomy in young beagle dogs