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

The collagenase produced by mesenchymal cells has been thought to have a great importance in the pathophysiology of connective tissue metabolism and prolongation of chronic inflammation. The factors, such as IL-1 and PMN factor, released by inflammatory cells have been known to induce mesenchymal cells to produce collagenase. In the present study, the collagenase activity of the nasal secretions were estimated using FITC-labelled collagens as substrates. The factor, enhancing the fibroblasts to produce collagenase, was also isolated from nasal secretions and partially characterized. The fibroblasts used in the present study were cultured with explant of the sections of nasal polyp obtained from a patient with chronic sinusitis. The collagenase activity in nasal secretions from patients with chronic sinusitis was high, whereas that of allergic nasal secretions was extremely low. Furthermore, the collagenase productions of nasal polyp-derived fibroblasts were enhanced by the extracts of nasal secretions from patients with chronic sinusitis. Crude extracts of nasal secretions were fractionated by ammonium sulfate precipitation. The active materials precipitated by 50% to 80% ammonium sulfate were further purified by Sephadex G-75 gel chromatography. The molecular weight determination of the active fraction checked by HPLC utilizing for TSK 2,000 SW gel column indicates 20,000 daltons for the active materials. However, the collagenase production of human microvascular endothelial cells derived from nasal mucosa was not enhanced by this factor. Although either the origin or the nature was not confirmed, the factor was considered to relate to the prolongation of chronic inflammation in the nasal and paranasal sinus pathology. Analysis of these factors will expected to establish methods for new therapeutics in chronic inflammation.
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PMID:[A study on collagenase production of nasal polyp-derived fibroblasts stimulated by nasal secretions of chronic sinusitis]. 254 27

Ro 23-6457, (all-E)-3,7-dimethyl-9-[2-(trifluoromethyl)-6-(nonyloxy)phenyl]-2, 4,6,8- nonatetraenoic acid, and Ro 23-2895, (all-E)-9-[2-(nonyloxy)phenyl]-3,7-dimethyl-2,4,6,8-nonatetraen oic acid, are two novel retinoid analogs which exhibit antiinflammatory activity in both the developing and the established rat adjuvant arthritis models [8]. Here we investigated the effect of these two compounds on the production of arachidonic acid (AA) metabolites in two in vitro test systems [i.e., Ca2+ ionophore A23187 (I)-stimulated resident rat peritoneal macrophages (MO) and cytokine-stimulated human dermal fibroblasts (HDF)]. Both compounds, Ro 23-6457 and Ro 23-2895, significantly inhibited the release of 14C-AA metabolites and the production of LTB4, PGE2, and 6-keto-PGF1 alpha in I-stimulated MO, at concentrations of 1-33 microM. Both compounds also inhibited the production of PGE2 in HDF stimulated by either rhuIL-1 alpha or huTNF alpha at concentrations of 1 x 10(-5) to 1 x 10(-7) M. Ro 23-2895 was also a potent inhibitor of IL-1-induced collagenase production in rheumatoid synovial cells (IC50 approximately 1 to 2.5 x 10(-8) M). The inhibitory profile of these novel compounds in these cell systems is therefore similar to that of other known antiinflammatory retinoids (e.g., all-trans- and 13-cis-retinoic acid). Inhibitory effects such as those described here might in part contribute to the antiinflammatory activity of these compounds in vivo.
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PMID:In vitro inhibition of arachidonic acid metabolism by two novel retinoid analogs. 255 63

The ability of the anabolic steroid, stanozolol, to stimulate procollagenase production by human synovial and skin fibroblasts was examined in an in vitro assay system. Stanozolol is used therapeutically to treat a variety of connective tissue and vascular disorders and its clinical effects suggest that it can modulate connective tissue breakdown. The results showed that stanozolol was capable, in a dose dependent manner, of significantly stimulating procollagenase production by skin fibroblasts. However, in three synovial fibroblast lines no evidence was found of increased collagenase production following treatment with stanozolol; although the synovial fibroblasts secreted significantly increased amounts of procollagenase in response to IL-1. These results may shed some light on the mechanism of action in vivo of stanozolol in the treatment of connective tissue disorders.
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PMID:The effect of the anabolic steroid, stanozolol, on the production of procollagenase by human synovial and skin fibroblasts in vitro. 255 1

A soluble product from cloned human T lymphocytes is capable of stimulating U937 cells, a line of human monocytes, to produce interleukin 1 (IL 1). We previously reported that U937 cells exposed to T lymphocyte-conditioned medium secrete mononuclear cell factor (MCF), which increases collagenase and prostaglandin E2 production by adherent rheumatoid synovial cells. Whereas structural and functional homologies between lymphocyte-activating factor (LAF, or IL 1) and MCF were described, previous attempts to measure LAF secretion by lymphokine-stimulated U937 cells were unsuccessful. Although the crude supernatants of cultured U937 cells exposed to medium from lectin-stimulated peripheral blood or cloned T lymphocytes contained MCF activity, no LAF activity was detected. After these crude supernatants were chromatographed on Ultrogel AcA54, however, and the fractions were individually assayed for IL 1, MCF and LAF activities were coeluted with apparent m.w. approximately 14,000 to 23,000. The inability to detect LAF activity in the unfractionated medium was accounted for by an inhibitor of lymphocyte proliferation present in fractions of higher m.w. The T lymphocyte product that stimulated U937 cell maturation and monokine production was secreted in response to lectin-stimulation in a dose-dependent fashion. Although we have previously demonstrated that the hormone 1,25-dihydroxyvitamin D3 caused maturational changes in U937 cells, and other investigators have reported effects of alpha and gamma interferon, these changes are dissociable from IL 1 production. Thus, a distinct lymphocyte-derived signal, necessary for the production of IL 1 by U937 cells, can be identified and dissociated from other biologic products that cause "maturational" changes. The detection of LAF activity in U937 cell supernatants requires the removal of an inhibitor of lymphocyte proliferation.
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PMID:Interleukin 1 production by the human monocyte cell line U937 requires a lymphokine induction signal distinct from interleukin 2 or interferons. 257 47

To investigate the correlation between chorioamnionitis and premature rupture of membranes (PROM), the influence of human recombinant interleukin-1 alpha (hrIL-1) on the metabolism of glycosaminoglycans (GAGs) and collagen in cultured human chorionic cells was examined and the following results were obtained. 1. When chorionic cells were incubated with D-[6-3H] glucosamine, the cells biosynthesized and rapidly secreted GAGs into the medium. After a 24-hr incubation, approximately 75% of total GAGs was distributed in the medium fraction, and more than 75% of these GAGs were found to be a high mol. wt (more than 1 x 10(6] hyaluronic acid. 2. hrIL-1 enhanced the biosynthesis and secretion of hyaluronic acid in a dose dependent manner, but hrIL-1 did not change the mol. wt of hyaluronic acid. In addition, no remarkable effect of hrIL-1 was exerted on the biosynthesis of the sulfated GAGs, therefore the consequential decrease in their relative concentrations was observed. 3. Collagen biosynthesized by chorionic cells increased linearly in proportion to the incubation period, and after a 12-hr incubation, about 75% of the tritilated collagen was secreted into the medium fraction. hrIL-1 did not modulate production of the collagen and noncollagenous protein in the cells. 4. hrIL-1 induced collagenase production in chorionic cells and significantly accelerated its production in a dose dependent manner, without affecting cell proliferation. The stimulatory effects of IL-1 on the biosynthesis of hyaluronic acid and collagenase are connected with the decrease in tensile strength observed in PROM. Thus, it is proposed that IL-1 from effused leukocytes in fetal membrane plays an important role in PROM with chorioamnionitis.
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PMID:[Effect of human recombinant interleukin-1 alpha on glycosaminoglycan and collagen metabolism in cultured human chorionic cells]. 259 17

Inflammatory and 'non-inflammatory' forms of arthritis affect a large proportion of the population and these diseases can often lead to disability. Although the pain of arthritis can be relieved to some extent by the peripherally acting aspirin-like drugs, the progression of disease leading to joint destruction is largely resistant to current drug therapy. The synovial joints of patients with rheumatoid arthritis are infiltrated with neutrophils, macrophages and lymphocytes and the resident cells become activated to degrade the cartilage and bone. The inflammatory and destructive changes that occur are brought about by the action of mediators or local hormones which are produced by a variety of cell-types. Lipid mediators, such as prostaglandins, contribute to the symptoms of arthritis while polypeptide cytokines, such as interleukin 1 and tumour necrosis factor, play a key role in joint destruction by activating the synovial cells and chondrocytes to release metalloproteinases, such as collagenase. Aspirin-like drugs inhibit the production of prostaglandins from inflamed tissues and thereby blunt the symptoms of arthritis. However, these drugs do not suppress the production of collagenase from connective tissue cells and, therefore, do not halt the degeneration of joint tissues.
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PMID:Pathogenesis and treatment of chronic arthritis. 269 74

Although it has been reported that interleukin 1 (IL-1) stimulate chondrocytes to produce collagenase and proteoglycanase in vitro, IL-1 producing cells and the function of IL-1 have not been demonstrated in osteocartilaginous tissue in vivo. Immunohistochemical studies of human cartilaginous epiphysis and growth cartilage demonstrated that IL-1 was detected in: (1) chondrocytes surrounding cartilage canal, (2) hypertrophic chondrocytes in cartilaginous epiphysis, (3) chondrocytes at the hypertrophic and calcified zones in the growth cartilage of actively growing bone. In contrast, few hypertrophic chondrocytes showed positive reactions to IL-1 in growth plates nearing physiologic closure. Furthermore, IL-1 was detected in chondrocytes cultured from human growth cartilage. These results show that IL-1 is produced by matured chondrocytes of human growth cartilage in vivo. Chondrocyte-derived IL-1 might play a key role in the hypertrophy of chondrocytes, in the vascularization of cartilage and in the formation of bone.
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PMID:Immunohistochemical localization of interleukin 1 in human growth cartilage. 279 32

Articular chondrocytes cultured in the presence of recombinant human interleukin 1 alpha (rhIL-1 alpha) or recombinant human tumor necrosis factor alpha (rhTNF alpha) caused increased production of the latent metalloproteinase (collagenase and caseinase) and the proteoglycan release from cartilage. The existences of IL-1 and TNF alpha in the chondrocytes of human articular cartilage were also shown by immunohistochemical staining using polyclonal antibodies. Furthermore, chondrocyte was found to be a producer of interleukin 6 (IL-6), known as a pleiotropic cytokine and thought to be an important mediator of the cell interactions in arthritis. In addition, the production of IL-6 was also shown to be stimulated by rhIL-1 alpha or rhTNF alpha. From our findings, we suggest there exists a very complicated autocrine control system of chondrolysis by the chondrocyte itself.
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PMID:The role of cytokines in chondrocyte mediated cartilage degradation. 281 Feb 94

Crude endotoxin preparations from Haemophilus actinomycetemcomitans and Bacteroides gingivalis showed activity in the two principal bio-assays for interleukin 1--the lymphocyte activating factor assay and stimulation of chondrocyte collagenase synthesis. Lipopolysaccharides purified from the crude endotoxins had reduced activity in the chondrocyte collagenase assay. The activity of the endotoxins may be due to synergic interaction between their lipopolysaccharides and other, as yet unidentified, bacterial components.
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PMID:The role of lipopolysaccharides in endotoxin-induced thymocyte proliferation and chondrocyte collagenase synthesis. 282 88

Osteoarthritis is characterized by a loss of articular cartilage due at least in part to the action of degradative enzymes secreted by chondrocytes. We have investigated the effect of type II collagen from cartilage and interleukin 1 on collagenase production in cultures of rabbit articular chondrocytes. Interleukin 1 alone stimulated the chondrocytes to secrete collagenase but this response was increased as much as fivefold by the addition of rabbit type II collagen. Bovine type II and chick type I collagens were also stimulatory. The native form of the collagens was not required since denatured collagens and purified chick type II alpha chains were effective. The observed effects of collagens and interleukin 1 may contribute to the progressive nature of osteoarthritis.
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PMID:The stimulation of collagenase production in rabbit articular chondrocytes by interleukin-1 is increased by collagens. 282 8


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