Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound   Target Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound

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Query: EC:3.2.1.17 (lysozyme)
21,489 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

We have studied cells dispersed with proteolytic enzymes from rheumatoid arthritic synovectomy specimens to determine the cell type(s) responsible for joint destruction. Initially 10-50% of these cells adhered to culture dishes within 24 hr and were of two main types: small, round cells and larger, stellate cells. During 1-4 days of culture, 5-25% had Fc receptors and 25-50% showed brisk phagocytosis. Daily producition, per 10(6) cells of collagenase (EC 3.4.24.3) (after trypsin pretreatment) was up to 70 mug of collagen fibrils lysed per min at 37 degrees (70 units), of prostaglandin (PGE2), up to about 1200 ng, and of lysozyme, up to about 100 mug. Under identical conditions of assay, fibroblasts grown from explants of synovium produced no detectable collagenase or lysozyme, and PGE2 was only 2-4 ng. With the dispersed cell preparations, macrophage markers (Fc receptors and lysozyme) were undetectable after 4 days and PGE2 decreased rapidly after about 7 more days. However, collagenase production continued for 3-25 weeks, and in some cultures, after cell passage. At these later stages, large, slow-growing stellate cells were predominant and could phagocytose carbon particles if incubated for greater than 6-8 hr. Indomethacin (14 muM) inhibited PGE2 but stimulated collagenase production whereas dexamethasone (10 nM) inhibited both. Production of PGE2 and collagenase in large amounts in vitro by these cells suggests that they may be involved in joint destruction in vivo. The precise origin of these synovial cells and the mechanisms responsible for the sustained production of collagenase at a high rate remain unidentified.
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PMID:Production of collagenase and prostaglandins by isolated adherent rheumatoid synovial cells. 17 63

With the ferret liquid-filled trachea in vitro, intraluminal methacholine (MCh), phenylephrine (PE) and histamine (Hist) increased smooth muscle tone and salbutamol (Salb) decreased tone. Lysozyme output was increased by intraluminal MCh and PE. Albumin transport into the lumen was not altered by intraluminal Hist, Salb or PE. The concentration-response curves for smooth muscle contraction and for lysozyme output to extraluminal MCh lay to the left of those for intraluminal MCh. Indomethacin shifted the smooth-muscle response curves to MCh significantly to the left but did not significantly alter lysozyme output. Extraluminal MCh produced a concentration-dependent increase in albumin output whilst intraluminal MCh did so in one of three studies. Albumin output in response to MCh was not significantly altered by indomethacin. Thus, MCh has a less potent effect on smooth muscle and lysozyme secretion and, to a lesser extent, on epithelial albumin transport when given intraluminally. This may be because the epithelium restricts diffusion of the drug or due to the production of a non-prostanoid factor which inhibits smooth muscle responsiveness. Smooth muscle responsiveness is enhanced by blocking cyclooxygenase activity, suggesting MCh-induced release of a prostanoid with relaxant activity.
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PMID:The effects of intraluminal and extraluminal drug application on secretion and smooth muscle tone in the ferret liquid-filled trachea in vitro. 144 38

Fibronectin secreted by macrophages may contribute to the development of pulmonary fibrosis. Prostaglandins are important regulators of macrophage metabolism whose role in the regulation of fibronectin production is not known. In this study, we examined the effects of PGE1 and indomethacin on human monocyte-derived macrophages exposed to these agents in culture for 10 to 14 days. Indomethacin (10 micrograms/ml) reduced the ratio of supernatant fibronectin to adherent cell DNA by 32%, p < 0.01, and reduced lysozyme/DNA by 29%, p < 0.0001. Exogenous PGE1 (1 ng/ml) did not affect fibronectin, but increased lysozyme/DNA by 27%, p < 0.01. In additional experiments, supernatant fibronectin and total protein synthesized in the presence of 3H-leucine were measured. Indomethacin (10 micrograms/ml) had no effect on total supernatant protein radioactivity, but reduced fibronectin/DNA by 33%, p < 0.001, and reduced fibronectin/total protein by 19%, p < 0.01. Since indomethacin increases macrophage secretion of plasminogen activator and interleukin-1, these experiments add to the evidence that specific secretory products of macrophages are regulated independently. We conclude that indomethacin at 10 micrograms/ml decreases the production of fibronectin and lysozyme by monocyte-derived macrophages. The modest size of the effect, and its absence at lower doses of indomethacin, indicate that prostaglandins are unlikely to have a major role in the regulation of macrophage production of fibronectin.
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PMID:Effects of indomethacin and prostaglandin E1 on the production of fibronectin and lysozyme by monocyte-derived macrophages in vitro. 166 50

The addition of dexamethasone, prednisolone or cortisol (in order of efficacy) to human monocytes in culture produced dose-related increases in the synthesis rates of the complement components C1 inhibitor (C1-inh), factor B (B) and C2. In contrast, concentrations of C3 and lysozyme in the culture supernatants were decreased. Indomethacin stimulated synthesis of C1-inh, C2 and B, but had little effect on synthesis of C3 or lysozyme. The simultaneous addition of cycloheximide (2.5 micrograms/ml) abrogated the effects of dexamethasone on synthesis of C2, B and C1-inh, but the effect of indomethacin on the synthesis of these components was unchanged. These data suggest that protein synthesis is required for the effects of glucocorticoids on the synthesis of C2, B and C1-inh to occur. Dexamethasone and indomethacin increased the abundances of C1-inh mRNA, B mRNA and C2 mRNA in parallel with changes in the synthesis rates of these proteins. The changes in mRNA abundance were not transcriptional, but were shown to be due to increased mRNA stability. In contrast, dexamethasone decreased the expression of C3 and lysozyme by decreasing the rate of transcription of these genes. Indomethacin had no effect on transcription of the C3 and lysozyme genes. The half-lives of C3 mRNA, lysozyme mRNA and actin mRNA were not altered by dexamethasone or indomethacin. It is concluded that the effects of glucocorticoids on monocyte synthesis of C2, B and C1-inh are due to increased mRNA stability and may be related to inhibition of prostaglandin synthesis, as these effects are similar to those produced by indomethacin. The effects of dexamethasone on the synthesis of C3 and lysozyme differ from those on C2, B and C1-inh as they depend upon a decrease in gene transcription, which is not affected by indomethacin.
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PMID:Modulation of complement gene expression by glucocorticoids. 174 40

The effects of nonsteroidal anti-inflammatory agents on superoxide production and granule enzyme release by human polymorphonuclear leukocytes stimulated with either formyl-methionyl-leucyl-phenylalanine (fMet-Leu-Phe] or immune complexes were investigated. Cytochrome c reduction and the release of lysozyme, beta-glucuronidase, myeloperoxidase and gelatinase were measured. Auranofin, phenylbutazone, sulfasalazine and the phospholipase A2 inhibitor, 4-bromophenacyl bromide, strongly inhibited these responses in fMet-Leu-Phe stimulated cells, at concentrations below 50 microM. Indomethacin, piroxicam, mefenamic acid, primaquine and quinacrine at 50-250 microM were inhibitory. Up to 1 mM ibuprofen and chloroquine inhibited superoxide production but had little effect on degranulation. With cells stimulated by IgG aggregates (immune complexes), up to 1 mM ibuprofen, mefenamic acid and piroxicam did not inhibit either response. Indomethacin, phenylbutazone, sulfasalazine and primaquine inhibited, but considerably higher concentrations were required than with fMet-Leu-Phe. Quinacrine inhibited superoxide production equally well with both stimuli but inhibited enzyme release only with fMet-Leu-Phe. Only auranofin, 4-bromophenacyl bromide, and the weakly effective chloroquine exerted approximately the same effect with both stimuli. D-Penicillamine did not affect enzyme release with either stimulus and interfered in the superoxide assay. Gelatinase release induced by fMet-Leu-Phe was affected to the same extent, or slightly more, than release of the other granule enzymes. With immune complexes, there was only modest inhibition of gelatinase release by any of the drugs at 250-1000 microM. Our results reinforce previous observations that many anti-inflammatory drugs affect neutrophil functions, but their effects vary with stimulus. The relative insensitivity of immune complex-induced responses to most of the drugs must be taken into account when considering their mode of action.
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PMID:Inhibition by nonsteroidal anti-inflammatory drugs of superoxide production and granule enzyme release by polymorphonuclear leukocytes stimulated with immune complexes or formyl-methionyl-leucyl-phenylalanine. 303 27

When human neutrophils (PMNs) are activated by appropriate stimuli, they aggregate, generate superoxide anion (O2-) and secrete lysosomal enzymes. Pre-incubation of PMNs in vitro with the cyclo-oxygenase (COx) inhibitor piroxicam (50 microM) before stimulation with the chemotactic peptide f-met-leu-phe (FMLP, 10(-7)M) inhibited all of these responses. The COx inhibitor ibuprofen inhibited FMLP-induced aggregation and lysozyme secretion, leaving O2- generation unaffected. Binding of 3H-FMLP was inhibited by piroxicam. When the plant lectin concanavalin A (Con-A, 30 micrograms/ml) or the tumor promoter phorbol myristate acetate (PMA, 50 micrograms/ml) was used as a stimulus, ibuprofen had no effect on PMN response, while piroxicam inhibited only O2- generation. To determine whether such inhibition might also occur in vivo, we tested neutrophil aggregation and O2- generation in response to FMLP in 26 normal subjects. These subjects were then administered therapeutic doses of piroxicam (20 mg/day), ibuprofen (2400 mg/day) or indomethacin (100 mg/day), and neutrophil functions were retested after 3 days. Piroxicam inhibited FMLP-induced aggregation by 31% (5.2 cm2/min versus 3.6 cm2/min, P less than 0.004) and O2- generation by 35% (15.8 nmol cytochrome c reduced versus 10.2 nmol, P less than 0.002). Ibuprofen inhibited FMLP-induced aggregation by 44% (5.2 versus 3.0, P less than 0.03) but had no effect on O2- production. Indomethacin inhibited FMLP-induced aggregation (6.4 versus 2.9, P less than 0.01) but had no effect on O2- generation.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:The inactivation of the polymorphonuclear leukocyte by non-steroidal anti-inflammatory drugs. 609 Mar 11

Indomethacin (0.5 mg/100 g b.w./day) and chloramphenicol (0.5 mg or 15 mg/100 g b.w./day) were tested for their anti-inflammatory effects on 7th day carrageenan-induced granuloma formation. Neither of the drugs modified granuloma or pouch wall weight but they decreased the exudate and the cluster of dead cells. Indomethacin and chloramphenicol decreased glucosamine in the dead cell granuloma fraction and increased the level of collagen in the pouch wall. The drugs differed in their inhibitory effect on lysozyme and prostaglandin E2 accumulation in the exudate. The increase in collagen was related to a drop in the level of prostaglandin E2 which seems to regulate collagen deposition in the granuloma. However, the prostaglandin E2-lysozyme correlation--which was only significant with chloramphenicol--suggests a mode of action for chloramphenicol different from that of indomethacin. Chloramphenicol could act by a myelodepressive and/or chemotactic effect. The effects of chloramphenicol on the macrophages are discussed.
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PMID:The effects of locally injected antibiotic on carrageenan-induced granuloma in rats. 623 83

Inhibition of prostaglandin synthesis at the time of antigen presentation was used to test the role of prostaglandins in the inductive stage of the in vivo immune response to several antigens. Indomethacin and Ro 20-5720, two prostaglandin synthesis inhibitors, produced a several-fold enhancement of the primary immunoglobulin (Ig) M and IgG anti-sheep red blood cell plaque-forming cell (PFC) response in CAF1 mice. Indomethacin and Ro 20-5720 also enhanced the antibody response to chicken serum albumin (CSA) in buffered saline. However, the antibody response to CSA in Freund's adjuvant was reduced by indomethacin treatment. Indomethacin treatment enhanced the PFC response to a chicken lysozyme-lipopolysaccharide conjugate, and did not greatly affect the PFC response to pneumococcal polysaccharide. The allogeneic cytotoxic response to the El-4 tumor line was delayed by indomethacin treatment and, since this tumor does not synthesize prostaglandins, we speculate that prostaglandin synthesis by the host is important in the generation of a cytotoxic response to this tumor. It is concluded that the role of prostaglandins in the induction of the immune response varies, and can be proinductive or anti-inductive, depending on the eliciting antigen.
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PMID:Effects of prostaglandin synthesis inhibition on the immune response. 679 42

C3a-induced lysosomal enzyme secretion from human peripheral neutrophils in a noncytolytic, dose-dependent (10-100 microgram/ml) process. Release of both primary and secondary granule constituents occurred when neutrophils were exposed to C3a plus cytochalasin B, however, C3 alone induced limited release of lysozyme. A competitive antagonist of the formyl-peptide receptor on neutrophils, t boc (phe-leu) 2-phe, did not block the release induced by C3a. Arachidonic acid antagonists, nordihydroguaiaretic acid and quercetin caused dose-dependent inhibition of release induced by C3a plus cytochalasin B, however, lysozyme release induced by C3a in the absence of cytochalasin B was minimally affected. Indomethacin at high concentration (greater than 10(-5) M) had similar inhibitory effects.
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PMID:C3a-induced lysosomal enzyme secretion from human neutrophils: lack of inhibition by f met-leu-phe antagonists and inhibition by arachidonic acid antagonists. 680 Sep 60

Retinoic acid induced lysozyme activity in mouse myeloid leukemia M1 cells. It also stimulated the synthesis and release of prostaglandins such as prostaglandin F2alpha, E2, and D2 by the cells. The particulate fraction of retinoic acid-treated M1 cells converted arachidonate to prostaglandins, and this conversion was almost completely inhibited by indomethacin. Retinol, retinal and retinyl acetate, but not the pyridyl analog of retinoic acid, also induced lysozyme activity and stimulated synthesis and release of prostaglandins. Indomethacin inhibited the induction of lysozyme activity by retinoic acid. The induction of lysozyme activity and the stimulation of prostaglandin E2 production were dependent on the concentration of retinoic acid. Kinetic studies showed that stimulation of prostaglandin E2 production by retinoic acid was followed by induction of lysozyme activity. The tumor promotor 12-O-tetradecanoyl-phorbol-13-acetate (TPA) and phorbol 12,13-didecanoate inhibited the induction of lysozyme activity by retinoic acid, but 4 alpha-phorbol didecanoate and phorbol did not. TPA and phorbol 12, 13-didecanoate, but not 4 alpha -phorbol didecanoate, also inhibited the stimulation of prostaglandin E2 production by retinoic acid. These results suggest that stimulation by retinoic acid of prostaglandin E2 production in M1 cells is a prerequisite for the induction of lysozyme activity. On the other hand, both retinoic acid and TPA inhibited the induction by dexamethasone of phagocytic activity, which is a typical functional marker of differentiation of M1 cells, without causing significant growth inhibition. Suboptimal concentrations of retinoic acid and TPA had synergistic inhibitory effects on the induction of phagocytic activity of M1 cells by dexamethasone.
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PMID:Stimulation by retinoic acid of prostaglandin production and its inhibition by tumor promoters in mouse myeloid leukemia cells. 694 53


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