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)

Influence of human recombinant interleukin-1 (hrIL-1) on collagen metabolism was investigated with rabbit uterine cervical fibroblasts. Enzyme-linked immunosorbent assays for collagenase and tissue inhibitor of metalloproteinases (TIMP) indicated that hrIL-1 participates in both stimulation of procollagenase production and suppression of TIMP synthesis by uterine cervical cells. IL-1 did not modulate collagen synthesis. In addition, the sensitivity to IL-1 of uterine cervix from ovariectomized rabbits was augmented by estradiol-17 beta treatment. Thus it is proposed that IL-1 accelerates collagenolysis in the cervical tissue and its effect on uterine cervix is hormonally regulated.
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PMID:Human recombinant interleukin-1 alpha-mediated stimulation of procollagenase production and suppression of biosynthesis of tissue inhibitor of metalloproteinases in rabbit uterine cervical fibroblasts. 283 71

Three human cell lines derived from oro-pharyngeal squamous cell carcinomas of the head were investigated for bone-resorbing activity in vitro. Culture media from all three spontaneously produced a non-dialysable osteolytic factor with activity in three in vitro assays for interleukin 1 (IL1), viz. the lymphocyte activating factor (LAF) assay, stimulation of collagenase synthesis by articular chondrocytes, and stimulation of prostaglandin E2 synthesis by fibroblasts. Addition of anti-human IL1 antibody to the culture media abolished all the bone-resorbing activity. Fractionation of the cell culture media by high performance liquid chromatography (HPLC) showed a single peak of activity in the chondrocyte assay with an apparent mol.wt of 15-17,000. This co-eluted with activity in a preparation of IL1 from rat peritoneal macrophage cultures. These results indicate that IL1 is responsible for the prostaglandin-independent bone resorbing activity synthesised by these cells in vitro, and may contribute to the bone destruction associated with the tumour.
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PMID:Macromolecular osteolytic factor synthesised by squamous carcinoma cell lines from the head and neck in vitro is interleukin 1. 284 18

Long-term synovial fibroblast cultures were exposed to interleukin 1 (IL-1) or prostaglandin E2 (PGE2). The normally spindle-shaped fibroblasts changed to stellate-shaped cells, resembling the HLA-DR-positive, collagenase-producing cells which are normally seen only in primary cultures from enzyme-digested rheumatoid synovial tissue. However, the IL-1- or PGE2-induced fibroblasts were not HLA-DR-positive. This suggests that these cell populations represent originally different cell lines or that the expression of HLA-DR antigens is not induced by the agents used. For further characterization of these stellate cells, the location of fibronectin and type I collagen was studied by specific antibodies and the pericellular coat around fibroblasts was visualized by the erythrocyte exclusion method. Both IL-1 and PGE2 treatments destroyed the intercellular fibronectin network. Type I collagen was detected as intracellular granules. The stellate fibroblasts were usually full of these granules in contrast to intact fibroblasts in which the number of collagen fluorescence granules varied greatly. The pericellular coat known to be formed mainly by hyaluronic acid was similar around spindle and stellate-shaped fibroblasts. Rheumatoid arthritis-derived fibroblasts did not differ from their non-rheumatoid counterparts in any of the experiments. The effect of IL-1 and PGE2 on fibroblasts simulates the interaction between mononuclear cells and fibroblasts in synovial stroma and also potentially the interactions between different cell types in synovial lining.
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PMID:Connective tissue components in synovial fibroblast cultures exposed to interleukin 1 and prostaglandin E2. 287 May 82

We investigated the ability of the human lymphokine leukocyte inhibitory factor (LIF) to modulate neutrophil-endothelial cell (EC) adherence. EC were cultured from collagenase-treated human umbilical cord veins and grown in complete medium supplemented with EC growth factor. Adherence was measured as the percent of 51Cr-labeled neutrophils remaining adherent to the EC after gentle lavage. Polymorphonuclear neutrophils (PMN) were pretreated with LIF (0.5 to 8 U/ml), extensively washed, and allowed to interact with the EC monolayers. LIF was demonstrated to induce an increase in the capacity of PMN to bind EC in a dose-dependent fashion (from 30.9 +/- 2.1% adherence with control-treated PMN to 68.6 +/- 3.0% at 4 U LIF; p less than 0.001). In subsequent experiments we demonstrated that 10 min was a sufficient preincubation time for LIF to modulate the capacity of the PMN to adhere to EC. LIF has previously been observed to up-regulate expression of C receptor type 3 on PMN, a receptor which has been shown to be involved in PMN-EC binding. Exposure of PMN to anti-C receptor type 3 antibody before their incubation with LIF abrogated its effect as did inactivation of LIF by an esterase inhibitor. We also investigated the ability of LIF to stimulate EC to bind untreated PMN. EC were pretreated with LIF (0.25 to 4 U/ml), extensively washed, and adherence measured as before. LIF was shown to induce a dose-dependent increase in the capacity of the EC to bind PMN (from 28.8 +/- 3.1% for untreated EC to 91.1 +/- 4.0% at 4 U LIF; p less than 0.001). Modulation of EC function required a minimum of 30 min and was inhibited in the presence of cycloheximide or actinomycin D. Neither anti-TNF-alpha or -beta antibodies nor polymixin B abrogated the augmentation by LIF. However, anti-IL-1 antibody partially inhibited the stimulation of EC adhesiveness by LIF, suggesting the possible involvement of this cytokine. These studies provide further evidence that LIF may mediate an important pro-inflammatory role in vivo.
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PMID:Leukocyte inhibitory factor stimulates neutrophil-endothelial cell adhesion. 297 37

Biosynthesis of the glycoprotein tissue inhibitor of metalloproteinases (TIMP) by human fibroblasts in culture has been characterized by functional assays, immunoprecipitation, and immunocytochemistry with a monospecific antiserum. As determined by radiolabeling with [35S]methionine, immunoprecipitation, and analysis by sodium dodecyl sulfate-polyacrylamide gel electrophoresis, the secreted form of TIMP had an Mr of 29,000, whereas the form associated with the cell layer had an Mr of 24,000. Unstimulated human lung fibroblasts (HFL-1) secreted TIMP at the rate of approximately 2 micrograms/10(6) cells/24 h, and normal foreskin fibroblasts (HS 27) and skin fibroblasts from a patient with Hurler's disease (GM 1391) secreted TIMP at 0.3 and 0.2 micrograms/10(6) cells/24 h, respectively. Secretion of TIMP was stimulated up to 10-fold by treating the cells with 20-100 ng/ml of 12-O-tetradecanoylphorbol 13-acetate or 10 units/ml of human interleukin 1. In the stimulated HFL-1 cells, TIMP accounted for 0.03-0.09% of the total [35S]methionine incorporated into protein, and 0.3-0.8% of the [35S]methionine in secreted protein. Although TIMP accounted for a relatively small proportion of total protein synthesis of the fibroblasts, greater than 80% of untreated and greater than 95% of stimulated fibroblasts synthesized TIMP, as determined by indirect immunofluorescence. The treatments of the human fibroblasts that increased TIMP secretion also induced synthesis and secretion of proenzyme forms of collagenase, indicating that degradative enzymes and their controlling inhibitors may be synthesized in parallel under certain conditions.
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PMID:Biosynthesis of tissue inhibitor of metalloproteinases by human fibroblasts in culture. Stimulation by 12-O-tetradecanoylphorbol 13-acetate and interleukin 1 in parallel with collagenase. 298 48

Marked connective tissue remodelling involves both destruction and repair in inflammatory lung diseases. Throughout the remodelling event, it was reasoned that alveolar macrophages may release substances similar to those produced by blood monocyte-macrophages that affect fibroblast functions, ie, the interleukin 1 family of monokines (or cytokines). We have examined human alveolar macrophage cultures obtained after bronchoalveolar lavage of freshly excised lungs from heavy smokers with bronchial carcinoma. Crude culture media contained fibroblast proliferative activity and collagenase- and PGE2- production-stimulating activity. The main peak of these biological activities was located around approximately 18 kilodaltons (kD) on gel filtration chromatography. Resolution of this peak by high performance liquid chromatography showed the presence of three distinct peaks, with quantitative and qualitative differences in biological activities. This suggests the presence of heterogeneous factors.
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PMID:Cultured human alveolar macrophages from smokers with lung cancer: resolution of factors that stimulate fibroblast proliferation, production of collagenase, or prostaglandin E2. 298 4

The objective of these studies was to examine the ability of phorbol myristic acetate (PMA), Fc fragments, and various forms of immune complexes to induce the production by human monocytes of factors stimulatory to chondrocytes or thymocytes. All of these materials were prepared free of detectable contamination with bacterial lipopolysaccharides (LPS) at the level of less than 0.1 ng/ml. Supernatants and lysates from stimulated human monocytes were assayed for their ability to induce collagenase production in cultured rabbit articular chondrocytes or to augment mitogen-induced proliferation of murine thymocytes. The activity detected by these assays exhibited an m.w. of approximately 15,000, and electrophoretic heterogeneity in the pH ranges of 5 to 5.5 and 6.5 to 7.0, characteristics of human interleukin 1 (IL 1) or IL 1-like factors. Monocytes cultured with 2 ng/ml LPS produced chondrocyte and thymocyte stimulatory factors. PMA, Fc fragments, and soluble, precipitated, particulate, or adherent immune complexes were inactive in stimulating the monocytes. However, complement fixation by precipitated immune complexes did generate activity capable of inducing monocytes to synthesize and secrete chondrocyte and thymocyte stimulatory factors. Adherent immune complexes and PMA were biologically active, as evidenced by induction of superoxide generation in the human monocytes. Supernatants from monocytes cultured on adherent immune complexes contained a factor inhibitory to chondrocyte and thymocyte responsiveness. This factor had a m.w. approximately 22,000 and appeared to inhibit specifically IL 1 stimulation, not interleukin 2 stimulation or cell proliferation. It was concluded that PMA, Fc fragments, and various forms of immune complexes in the absence of complement do not induce IL 1 production in human monocytes. However, complement fixation by immune complexes does lead to activation of monocytes to produce IL 1. Monocytes cultured on adherent immune complexes produce an IL 1 inhibitor.
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PMID:Effects of immune complexes on production by human monocytes of interleukin 1 or an interleukin 1 inhibitor. 298

Human PHA-stimulated mononuclear cells produce a factor which inhibits synovial cell collagen and non-collagen protein synthesis, whereas it enhances hyaluronic acid (HA) production. Indomethacin (10(-4)-10(-6) M), a cyclo-oxygenase inhibitor, suppresses this effect, suggesting that the mechanism is prostaglandin-mediated. The active material, of apparent molecular weight 12 000-20 000, also displays the properties of the mononuclear cell factor (MCF) previously described by others, since its stimulates collagenase and PGE2 release by the cultured synovial cells. Furthermore, it co-purifies with interleukin 1 (IL 1) as shown by lymphocyte-activating factor activity. This strongly suggests that IL 1 could be responsible for some (or all) the effects observed on MCF-exposed synovial cells. From these data, we deduce the possibility that mononuclear cells may participate in limiting synovial collagen deposition in rheumatoid arthritis.
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PMID:Mononuclear cell-mediated modulation of synovial cell metabolism. I. Collagen synthesis. 298 10

Adherent rheumatoid synovial cells produce and release into supernatant culture medium latent collagenase and PGE2. The levels of collagenase and PGE2 can be increased by a soluble factor present in mononuclear cell-conditioned medium, partially purified by gel-filtration, which has homologies with interleukin 1, and is produced by monocyte/macrophages. The synovial cell cultures produce collagens (procollagens) and fibronectin as well. The factor(s) present in the mononuclear cell conditioned medium which increases medium levels of collagenase PGE2 also stimulates synthesis of total protein as well as types I and III procollagen by the synovial cells. This stimulation by the monocyte factor is augmented in the presence of indomethacin, which blocks endogenous PGE2 production. Medium levels of fibronectin parallel those of procollagen. The addition of exogenous PGE2 abolishes the effect of indomethacin on collagen and fibronectin synthesis. These observations of mononuclear cell-mediated increases in fibronectin synthesis may account for the high levels of fibronectin found by others in rheumatoid synovium and synovial fluids as the increases in collagen synthesis might also explain the fibrosis observed in some rheumatoid joints.
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PMID:Mononuclear cell-conditioned medium containing mononuclear cell factor (MCF), homologous with interleukin 1, stimulates collagen and fibronectin synthesis by adherent rheumatoid synovial cells: effects of prostaglandin E2 and indomethacin. 298 54

Cultured human alveolar macrophages from smokers with lung cancer produced spontaneously variable amounts of factors stimulating fibroblast proliferation and production of prostaglandin E2 and collagenase by fibroblasts. These biological activities belong to molecules similar or identical to interleukin 1. Exogenous leukotriene B4 added to alveolar macrophage cultures increased the production of these factors. The Ca++ ionophore A23187 was found to have similar effects. By the control of monokine production, leukotriene B4 locally released by inflammatory cells may modulate lung fibroblast functions.
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PMID:Effects of LTB4 and Ca++ ionophore A23187 on the release by human alveolar macrophages of factors controlling fibroblast functions. 299 Apr 59


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