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)

To investigate the mechanism of cyclosporine (Cs)-induced fibrous gingival enlargement, the indirect effects of Cs on fibroblast collagenolysis via the drug's effect on the synthesis of the fibroblast regulatory monokines interleukin-1 beta (IL-1 beta) and tumor necrosis factor-alpha (TNF alpha) have been studied. Peripheral blood monocytes stimulated with lipopolysaccharide (LPS) for 48 h produced conditioned media (MCM-LPS) that contained 665 pg/ml IL-1 beta and 16 pg/ml TNF alpha and significantly (P less than 0.001) enhanced the collagenase activity of a fibroblast strain (GN 23) derived from a healthy individual with clinically normal gingiva. The concurrent addition of Cs (50, 100, or 150 ng/ml) with LPS to the monocytes (MCM-LPS-Cs) significantly diminished their ability to enhance GN 23 collagenase activity in a dose-dependent manner, with MCM-LPS-Cs (150 ng/ml) causing the greatest effect. Cs also significantly inhibited IL-1 beta and TNF alpha production. Although the greatest inhibition of both cytokines was at 50 ng/ml Cs, the corresponding MCM-LPS-Cs caused the least diminution (16%) of the collagenase stimulation caused by MCM-LPS (no Cs). This suggested that factor(s) other than or in addition to IL-1 beta and TNF alpha might be responsible for the stimulation of GN 23 collagenase activity. MCM-LPS depleted of IL-1 beta by affinity chromatography retained its stimulatory effect on GN 23 collagenolysis, and human recombinant IL-1 beta and TNF alpha, when tested alone or together at levels found in the stimulatory MCM-LPS and MCM-LPS-Cs, did not stimulate GN 23 collagenase activity as did the crude conditioned media. This evidence suggested that the conditioned media contained the complex mixture of cytokines necessary to stimulate collagenase activity of this fibroblast strain and that IL-1 beta and TNF alpha were not necessarily involved. Cs may alter the synthesis of other collagenase-stimulating cytokines, accounting for the diminished ability of Cs-treated monocytes to enhance collagenase activity of susceptible fibroblast strains. Decreased collagenase activity, therefore, resulting from Cs suppression of monokine production, may be an important factor in the development of fibrous gingival enlargement seen in some susceptible patients treated with Cs.
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PMID:Interleukin-1 beta- and tumor necrosis factor-alpha-independent monocyte stimulation of fibroblast collagenase activity. 196 53

To clarify the role of leukocytes effused into uterine cervix at term pregnancy, the effect of conditioned medium (MCM) of rabbit peritoneal macrophages on the production of specific collagenase by cervical cells was investigated, in vitro. MCM stimulated uterine cervical cells to induce a 10-fold increase in collagenase production as compared with the control. Similarly, production of gelatinolytic metalloproteinase (an endogenous procollagenase activator) increased to about 4-fold of the control cultures, whereas MCM did not affect [3H]thymidine incorporation into DNA. The enhancement of collagenase production was depressed by the treatment of cells with 10(-6) M cycloheximide. The MCM also contained lymphocyte-activating activity (interleukin-1). These data suggest that rabbit uterine cervical cells are able to produce both specific collagenase and gelatinolytic metalloproteinase in response to interleukin-1, and that leukocytes effused into the cervix may participate in the ripening and dilation of uterine cervix at term pregnancy.
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PMID:The role of leukocyte factors on uterine cervical ripening and dilation. 282 21

Recent work from this laboratory has shown that macrophages in culture synthesize and secrete a soluble factor(s) that induces the synthesis of collagenase in primary cultures of rabbit chondrocytes (Arth. Rheum. 23, 448, 1980). The current studies were undertaken to determine the role of arachidonate metabolism in this process. Incubation of chondrocytes with MCM (Macrophage Conditioned Medium) and low doses of indomethacin (1-10 microM) had no effect on collagenase synthesis. The lipoxygenase inhibitor NDGA, indomethacin at high doses (50 microM), diethylcarbamazine and the phospholipase inhibitor dibromoacetophenone, inhibited the MCM dependent synthesis of collagenase in chondrocytes. These inhibitors did not affect collagenase activity nor did they interfere with the activation of latent collagenase. Our data indicate that although cyclooxygenase plays no role in the MCM dependent induction of collagenase in chondrocytes, lipoxygenase activity may be essential.
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PMID:Studies on the effects of cyclo-oxygenase and lipoxygenase inhibitors on the macrophage stimulated synthesis of collagenase by rabbit chondrocytes. 300 57

Monolayer cultures of rabbit chondrocytes were stimulated to produce collagenase with conditioned medium from human peripheral blood mononuclear cells (MCM), and the ability of Razoxane to modulate the production of collagenase and specific tissue inhibitor of metalloproteinases (TIMP) was studied. Collagenase production was inhibited and TIMP increased by Razoxane, in a dose-dependent manner, when cells were treated daily for 3 days. Over this period the effect of Razoxane was progressive; 50 micrograms/ml or less had no effect at day 1 but 50 micrograms/ml was effective by day 3. The effectiveness of Razoxane was inversely related to the degree of MCM stimulation and the confluency of the culture. On removal of the drug, chondrocytes stimulated with MCM recovered their ability to produce collagenase, and TIMP production returned to near normal. The results suggest that the ability of Razoxane to reduce collagenase and increase TIMP production may correlate with its effectiveness in treating psoriatic arthritis.
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PMID:The effects of razoxane (ICRF 159) on the production of collagenase and inhibitor (TIMP) by stimulated rabbit articular chondrocytes. 631 74

Bone resorption is a complex multistep process that involves removal of both the organic and mineral constituents of bone matrix by proteolytic enzymes synthesized by osteoblasts and osteoclasts. To further understand the role of matrix metalloproteinases (MMPs) and their specific inhibitors TIMPs (tissue inhibitor of metalloproteinases) in this process, human osteoblasts were obtained by sequential enzymatic digestion from samples of bone from normal donors and patients with various forms of arthritis; first passage cells were used in all experiments and cultured on a type I collagen substratum. Collagenase was detected by an ELISA in supernatants from unstimulated osteoblasts (range 12-730 ng/mL), although the levels did not appear to bear any relationship to the age or clinical status of the patient; treatment with parathyroid hormone (PTH; 2 units/mL) and 1,25-dihydroxyvitamin D3 [1,25(OH)2D3, 10 ng/mL] had no added effect, but mononuclear cell conditioned medium (MCM; 5% v/v) and interleukin-1 alpha (IL-1 alpha; 1 ng/mL) both stimulated collagenase synthesis, in the case of MCM by two orders of magnitude. TIMP-1 was detected in unstimulated cultures by an ELISA (range 320-590 ng/mL), the mean level being three-fold greater than for collagenase and was stimulated by 1,25(OH)2D3 and MCM treatment. Degradation studies showed that, over a 120 h culture period, one third of the collagen substratum was degraded by unstimulated cells. PTH and 1,25(OH)2D3 had no effect on this endogenous level of lysis, but addition of MCM and IL-1 alpha resulted in a significant increase in collagen degradation.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:The synthesis of collagenase, gelatinase-A (72 kDa) and -B (95 kDa), and TIMP-1 and -2 by human osteoblasts from normal and arthritic bone. 854 Nov 38