Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:3.2.1.31 (beta-glucuronidase)
 7,680 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Murine peritoneal macrophages were treated with interferon-gamma (IFN-gamma) or tumor necrosis factor-alpha (TNF). Measurements of changes in acid phosphatase and beta-glucuronidase levels were made as an indication of activation by cytokine treatment. IFN-gamma or TNF-gamma treatment resulted in a significant increase in the activities of both enzymes measured in the cell lysates. This increase was observable after 6 h of incubation, but reached its maximum level after 24 h of incubation. The effect of the treatment of the cells with both cytokines together was additive. No synergistic effect of addition of both cytokines on the enzyme levels was observed.
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PMID:Effects of interferon-gamma and tumor necrosis factor-alpha on macrophage enzyme levels. 249 94

This study examined the properties and responsiveness to cytokines of macrophages purified from normal and nephritic glomeruli to ascertain whether macrophages activated in vivo develop programmed unresponsiveness to cytokines as do bone marrow-derived macrophages in vitro when activated by interferon-gamma (IFN-gamma), tumor necrosis factor (TNF), interleukin-4 (IL-4), or transforming growth factor-beta (TGF-beta). Macrophages from normal glomeruli did not generate nitric oxide (NO) spontaneously but only after treatment with IFN-gamma and TNF-alpha. NO generation by these macrophages was abrogated by administering IL-4, TGF-beta, or TNF-alpha before but not after IFN-gamma treatment. Glomerular macrophages also expressed beta-glucuronidase, which was increased by TGF-beta and decreased by IFN-gamma and TNF. By contrast, glomerular macrophages from rats with nephrotoxic nephritis did not express beta-glucuronidase even after exposure to TGF-beta. Furthermore, they generated NO spontaneously, and this spontaneous generation of NO was not suppressed by IL-4, TGF-beta, or TNF-alpha. Systemic treatment of nephritic rats with IL-4 reduced NO generation by 40% but did not prevent activation, which is similar to the effect of IL-4 on bone marrow-derived macrophages in vitro when given simultaneously with IFN-gamma. We conclude that macrophages infiltrating inflamed glomeruli have developed programmed unresponsiveness to activating cytokines. This may enable them to function appropriately in the complex conditions within an inflammatory focus.
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PMID:Macrophages from inflamed but not normal glomeruli are unresponsive to anti-inflammatory cytokines. 1062 78

Tartrate-resistant acid phosphatase (TRAP) is a lysosomal di-iron protein of mononuclear phagocytes and osteoclasts. Hitherto, no role for the enzyme in immunity has been identified; however, knockout mice lacking TRAP have a skeletal phenotype caused by an intrinsic osteoclast defect. To investigate a putative function for TRAP in macrophages (Mphi), we investigated proinflammatory responses and systemic microbial clearance in knockout mice compared with age- and gender-matched congenic wild-type mice. Phorbol 12-myristate 13-acetate (PMA)-stimulated and interferon-gamma (IFN-gamma)-induced superoxide formation was enhanced in peritoneal Mphi lacking TRAP; nitrite production in response to stimulation with lipopolysaccharide (LPS) and IFN-gamma was also increased. In addition, secretion of the proinflammatory cytokines, tumour necrosis factor-alpha (TNF-alpha), interleukin (IL)-1beta and IL-12, was significantly greater in TRAP-deficient Mphi when stimulated with LPS, with or without addition of either TNF-alpha or IFN-gamma. The activity of tartrate-sensitive (lysosomal) acid phosphatase was increased in Mphi from the knockout mice but activities of the lysosomal hydrolases N-acetyl beta-glucosaminidase and acid beta-glucuronidase were unchanged, indicating selective activation of compensatory acid phosphatase activity. Evidence of impaired Mphi function in vivo was obtained in TRAP knockout mice, which showed delayed clearance of the microbial pathogen, Staphylococcus aureus, after sublethal intraperitoneal inoculation. After microbial challenge, peritoneal exudates obtained from TRAP knockout mice had a reduced population of Mphi. As peritoneal Mphi and neutrophils lacking TRAP were able to phagocytose and kill S. aureus normally in vitro, TRAP may directly or indirectly influence recruitment of Mphi to sites of microbial invasion. Our study shows that TRAP participates in the inflammatory response of the Mphi and influences effector signalling pathways in innate immunity.
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PMID:Mice lacking tartrate-resistant acid phosphatase (Acp 5) have disordered macrophage inflammatory responses and reduced clearance of the pathogen, Staphylococcus aureus. 1116 43

The purpose of this investigation was to determine the effects of bon narine treatment on macrophage and lymphocyte functions in mice. Twelve week-old female inbred BALB/c mice were given bon narine p.o. at 30 mg/kg per day and sacrificed after three months. Glucose consumption of peritoneal macrophages in the bon narine treated group during incubation up to 72 h was significantly higher than that in the control group. Activities of acid phosphatase (APH), beta-glucuronidase (GLU) and lactate dehydrogenase (LDH) in the peritoneal macrophages in the bon narine treated group significantly increased compared to that in the control group. Macrophage production of nitric oxide stimulated by lipopolysaccharide (LPS) in the bon narine treated group was significantly increased. Interleukin-1beta (IL-1beta) production of peritoneal macrophages stimulated by LPS was significantly higher in the bon narine treated group. Stimulation indices in splenic lymphocytes by concanavalin A (Con A) in the bon narine treated group were significantly higher than that in the control group. Interleukin-2 (IL-2) and interferon-gamma (IFN-gamma) production stimulated by Con A were significantly increased in the bon narine treated mice. Interleukin-4 (IL-4) production of splenic lymphocytes stimulated by Con A was not different in the control group and the bon narine treated group. These findings might suggest that oral administration of bon narine effectively enhanced the macrophage function and lymphocyte responsiveness in mice.
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PMID:Enhanced macrophage functions and cytokine production of lymphocytes after ingestion of bon narine in female BALB/c mice. 1119 48

The anti-inflammatory activities of the isolated flavonoids, quercetin 3-O-methyl ether (1), kaempferol (2), and quercetin (3), of Rhamnus nakaharai, and anthraquinone, frangulin B (4), of Rhamnus formosana, were assessed in vitro by determining their inhibitory effects on the chemical mediators released from mast cells, neutrophils, macrophages, and microglial cells. Compounds 1 - 3 strongly inhibited the release of beta-glucuronidase and lysozyme from rat neutrophils stimulated with formyl-Met-Leu-Phe/cytochalasin B (fMLP/CB). Compound 1 strongly inhibited superoxide anion formation in fMLP/CB or phorbol 12-myristate 13-acetate (PMA)-stimulated rat neutrophils. Compound 1 exhibited potent inhibitory effect on tumor-necrosis factor-alpha ( TNF-alpha) formation in lipopolysaccharide (LPS)-stimulated RAW 264.7 cells while 1 and 4 showed potent inhibitory effects on TNF-alpha formation in LPS/IFN-gamma (interferon-gamma)-stimulated murine microglial cell lines N9.
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PMID:In vitro anti-inflammatory effects of quercetin 3-O-methyl ether and other constituents from Rhamnus species. 1173 18

Some chalcones exert potent anti-inflammatory activities. 2',5'-Dialkoxychalcones and 2',5'-dihydroxy-4-chloro-dihydrochalcone inhibited nitric oxide (NO) production in lipopolysaccharide (LPS)/interferon-gamma (IFN-gamma)-activated N9 microglial cells and in LPS-activated RAW 264.7 macrophage-like cells have been demonstrated in our previous reports. These compounds also suppressed the inducible NO synthase (iNOS) expression and cyclooxygenase-2 (COX-2) activity in RAW 264.7 cells. In an effort to continually develop potent anti-inflammatory agent, a series of chalcones were prepared by Claisen-Schmidt condensation of appropriate acetophenones with appropriate aromatic aldehyde and then evaluated their inhibitory effects on the activation of mast cells, neutrophils, macrophages, and microglial cells. Most of the 2',5'-dihydroxychaclone derivatives exhibited potent inhibitory effects on the release of beta-glucuronidase and lysozyme from rat neutrophils stimulated with formyl-Met-Leu-Phe (fMLP)/cytochalasin B (CB). Some chalcones showed potent inhibitory effects on superoxide anion generation in rat neutrophils in response to fMLP/CB. Compounds 1 and 5 exhibited potent inhibitory effects on NO production in macrophages and microglial cells. Compound 11 showed inhibitory effect on NO production and iNOS protein expression in RAW 264.7 cells. The present results demonstrated that most of the 2',5'-dihydroxychaclones have anti-inflammatory effects. The potent inhibitory effect of 2',5'-dihydroxy-dihydrochaclones on NO production in LPS-activated macrophage, probably through the suppression of iNOS protein expression, is proposed to be useful for the relief of septic shock.
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PMID:Structure-activity relationship studies on chalcone derivatives. the potent inhibition of chemical mediators release. 1246 13

One new pterocarpanoid, crotafuran E (1), and three known compounds were isolated from the bark of Crotalaria pallida. The structure of 1 was determined by spectral methods. Two pterocarpanoids, crotafurans A (2) and B (3), previously isolated from this plant, showed significant concentration-dependent inhibitory effects on the NO production in lipopolysaccharide (LPS)-stimulated RAW 264.7 macrophage-like cells, with IC(50) values of 23.0 +/- 1.0 and 19.0 +/- 0.2 microM, respectively. Compound 3 also inhibited the LPS/interferon-gamma (IFN-gamma)-stimulated NO production in N9 microglial cells with an IC(50) value of 9.4 +/- 0.9 microM. Moreover, compound 2 produced a concentration-dependent inhibition of the release of beta-glucuronidase and lysozyme from rat neutrophils in response to formyl-Met-Leu-Phe/cytochalasin B (fMLP/CB) with IC(50) values of 7.8 +/- 1.4 and 9.5 +/- 2.1 microM, respectively.
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PMID:Anti-inflammatory constituents and new pterocarpanoid of Crotalaria pallida. 1266 1

Three novel phloroglucinol derivatives, garcinielliptones F (1), H (3), and I (4), and two novel terpenoids, garcinielliptones G (2) and J (5), with a new skeleton have been isolated from the seeds of Garcinia subelliptica. Their structures, including relative configurations, were elucidated by spectroscopic methods and computer-generated molecular modeling. Compound 1 showed potent inhibitory effects on the release of beta-glucuronidase and lysozyme from rat neutrophils that had been stimulated with formyl-Met-Leu-Phe (fMLP)/cytochalasin B (CB). This effect was concentration-dependent with IC(50) values of 26.9+/-2.6 and 20.0+/-1.3 microM, respectively. Compound 1 also showed a potent concentration-dependent inhibitory effect on superoxide anion generation in rat neutrophils stimulated with fMLP/CB, with an IC(50) value of 17.0+/-0.9 microM. Compound 4 showed a potent inhibitory effect on NO production in culture media of N9 cells in response to lipopolysaccharide (LPS)/interferon-gamma (IFN-gamma) in a concentration-dependent manner with an IC(50) value of 7.4+/-0.2 microM.
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PMID:Terpenoids with a new skeleton and novel triterpenoids with anti-inflammatory effects from Garcinia subelliptica. 1463 35

One new isoflavone, 5,7,4'-trihydroxy-2'-methoxyisoflavone (3) and seven, and four known compounds were isolated from the barks of Crotalaria pallida and the seeds of C. assamica, respectively. The known compounds, apigenin (1) and 2'-hydroxygenistein (2), isolated from C. pallida, showed significant concentration-dependent inhibitory effects on the release of beta-glucuronidase and lysozyme from rat neutrophils in response to formyl-Met-Leu-Phe/cytochalasin B (fMLP/CB) with IC(50) values of 2.8+/-0.1 and 17.7+/-1.9, and 5.9+/-1.4 and 9.7+/-3.5 microM, respectively. The known compounds, daidzein (4) and 2'-hydroxydaidzein (6), isolated from C. pallida, inhibited of the release of lysozyme and beta-glucuronidase from rat neutrophils in response to fMLP/CB with IC(50) values of 26.3+/-5.5 and 13.7+/-2.6 microM, respectively. Compounds 1 and 4 also showed significant concentration-dependent inhibitory effects on superoxide anion generation in rat neutrophils stimulated with fMLP/CB with IC(50) values of 3.4+/-0.3 and 25.1+/-5.0 microM, respectively. Compounds 1 and 5, previously isolated from C. pallida, showed the inhibition of NO production in lipopolysaccharide (LPS)-stimulated RAW 264.7 macrophages and LPS/interferon-gamma (IFN-gamma)-stimulated N9 microglial cells with IC(50) values of 10.7+/-0.1 and 13.9+/-1.1 microM, respectively. Flavonoids, suppressed chemical mediators in inflammatory cells, may have value in treatment and prevention of central and peripheral inflammatory diseases associated with excess production of chemical mediators.
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PMID:Anti-inflammatory flavonoids and pterocarpanoid from Crotalaria pallida and C. assamica. 1501 12

Three new phloroglucinols, garcinielliptones K (1), L (2), and M (3), and two new terpenoids, garcinielliptones N (4) and O (5), have been isolated from the seeds of Garcinia subelliptica. The structures of 1-5 including their relative configurations were elucidated by spectroscopic methods and supported by computer-generated molecular modeling. Compounds 2 and 3 showed potent inhibitory effects on the release of beta-glucuronidase, and on beta-glucuronidase and histamine, respectively, from peritoneal mast cells stimulated with p-methoxy-N-methylphenethylamine (compound 48/80) in a concentration-dependent manner. Compounds 2 and 3 showed potent effects on NO production in culture media of RAW 264.7 cells in response to lipopolysaccharide (LPS). Compound 2 also showed a potent effect on NO production in culture media of N9 cells in response to LPS/interferon-gamma (IFN-gamma).
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PMID:Anti-inflammatory phloroglucinols and terpenoids from Garcinia subelliptica. 1556 64


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