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:1.11.1.6 (catalase)
55,569 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Alveolar macrophages (AMs) were analyzed for ability to support replication of the intracellular bacterium Francisella tularensis live vaccine strain (LVS). AM supported in vitro growth (2 to 3 logs over 5 days) of LVS with a doubling time of 8 +/- 0.8 h. AMs were analyzed for responsiveness to rIFN-gamma for destruction of this lung pathogen. AM treated with 50 U/ml rIFN-gamma allowed early growth of bacteria (six doublings over 48 h) but between 48 and 96 h rIFN-gamma-treated AM eliminated 1.5 logs of LVS. AMs were sensitive to effects of rIFN-gamma; as little as 5 U/ml rIFN-gamma stimulated AM antimicrobial activity, with half-maximal activity 0.3 U/ml. rIFN-gamma-induced antimicrobial effects in AM correlated with amount of nitrites produced, but nitric oxide played only a minimal role in antibacterial effects induced in AM, because NG-MMLA (specific inhibitor of L-arginine-dependent nitric oxide production) failed to block antimicrobial activity of IFN-gamma-stimulated AM. IL-10, TGF-beta 1, and IFN-alpha (cytokines known to regulate effector functions of activated macrophages) also did not block anti-F. tularensis activity of IFN-gamma-stimulated AM. Reactive oxygen metabolites, depletion of tryptophan, and sequestration of iron did not contribute to anti-F. tularensis activity because addition of superoxide dismutase or catalase, excess iron, or tryptophan to IFN-gamma-treated AM did not reverse the anti-F. tularensis activity observed in these cells. Regulation of AM effector activity differed from that of other macrophage populations, in that while rIFN-gamma-stimulated AM produced TNF-alpha (100 U/ml at 72 h), TNF-alpha was not required as a costimulator for induction of antimicrobial activities by rIFN-gamma because anti-TNF-alpha treatment of rIFN-gamma-stimulated AM blocked TNF-alpha but had no effect on either production of nitrites or anti-F. tularensis activity.
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PMID:Nitric oxide-independent killing of Francisella tularensis by IFN-gamma-stimulated murine alveolar macrophages. 802 51

Mechanisms regulating the balance of T-helper 1 (Th1) and T-helper 2 (Th2) immune responses are of great interest as they may determine the outcome of allergic and infectious diseases. Recently, in mice, nitric oxide (NO), a powerful modulator of inflammation, has been reported to preferentially down-regulate Th1-mediated immune responses. In the present study, we investigated the effect of NO on the production of Th1- and Th2-associated cytokines by activated human T cells and human T-cell clones. Cytokine secretion was measured in the presence of the NO-donating agents 3-morpholinosydnonimine (SIN-1) and S-nitroso-N-acetylpenicillamine (SNAP). Both NO-donors markedly inhibited the release of interferon-gamma (IFN-gamma), interleukin-2 (IL-2), IL-5, IL-10 and IL-4 by anti-CD3 activated T cells. A preferential inhibition of Th1-associated cytokines was not observed. Neither was nitrite found in the supernatants of activated T cells, nor was specific mRNA for inducible and constitutive NO synthase detectable, indicating that T cells themselves did not contribute to the observed effect of the NO donors. Costimulation with anti-CD28 monoclonal antibodies (mAb) prevented SIN-1/SNAP-mediated down-regulation of cytokine production only in part. In contrast, when T cells were stimulated by phorbol-ester and ionomycin, they were refractory to SIN-1-induced inhibition of cytokine production. When SIN-1 was added after the onset of anti-CD3 stimulation, the inhibitory effect was found to be less pronounced, indicating that SIN-1 may interfere with early signal transduction events. The addition of superoxide dismutase (SOD) and catalase did not restore the effects of SIN-1, demonstrating that the inhibition of cytokines was due to NO and not to oxygen intermediates. Furthermore, 8-Br-cGMP-mediated increase of intracellular cGMP caused the same pattern of cytokine inhibition as observed with SIN-1 and SNAP. Using a single cell assay, these agents were shown to reduce the frequency of IFN-gamma-producing T cells, suggesting that not all T cells are susceptible to SIN-1/SNAP. However, cytokine production by purified T-cell subpopulations (CD4+, CD8+, CD45RA+, and CD45RO+) was equally impaired by NO donors. In conclusion, in contrast to the murine system, our results do not provide evidence that NO preferentially inhibits Th1-cytokine secretion of activated human T cells in vitro.
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PMID:Nitric oxide inhibits the secretion of T-helper 1- and T-helper 2-associated cytokines in activated human T cells. 913 48

Trauma patients develop a severe immunosuppression that includes suppression of natural killer (NK) cell activity although numbers of NK cells are not reduced. The mechanism of suppression of NK cell activity after major trauma is not known. The aim of the present study was to investigate the in vitro effect of plasma samples from trauma patients (TP) on the cytotoxic activity of normal NK cells. Buffycoat mononuclear cells (5x10(5)/well) were preincubated with either TP or plasma samples from age and sex matched healthy controls (CP) for 0, 16 or 40 h. These effector cells were then cultured with 51Cr labeled K-562 cells (2x10(4)/well) for 4 h at 37 degrees C and % lysis was calculated. No significant differences in % lysis between CP and TP were found with 0 or 16 h preincubation, however 40 h preincubation with TP severely suppressed NK cell function (p=0.003) as compared to preincubation with CP for the same period. Addition of neutralizing anti-IL-4, anti-TGF-beta1, or anti-IL-10 antibodies did not reverse the NK cell suppression. There was a partial reversal of NK cell suppression by catalase but not by SOD or L-NMMA. Removal of monocytes from buffycoat mononuclear cells also significantly reversed the NK cell suppression. These data suggest that suppression of NK cell activity in trauma patients may be an accessory cell dependent phenomenon and may partially depend on production of reactive oxygen metabolites (ROM).
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PMID:Mechanism of suppression of natural killer cell activity in trauma patients. 987 82

A spiral-shaped bacterium with bipolar, single-sheathed flagella was isolated from the intestines of IL-10 (interleukin-10)-deficient (IL-10(-/-)) mice with inflammatory bowel disease. The organism was microaerobic, grew at 37 and 42 degrees C, and was oxidase and catalase positive but urease negative. On the basis of 16S rRNA gene sequence analysis and biochemical and phenotypic criteria, the organism is classified as a novel helicobacter. Cesarean section-rederived IL-10(-/-) mice without helicobacter infection did not have histological evidence of intestinal inflammation. However, helicobacter-free IL-10(-/-), SCID/NCr, and A/JNCr mice experimentally inoculated with the novel urease-negative Helicobacter sp. developed variable degrees of inflammation in the lower intestine, and in immunocompetent mice, the experimental infection was accompanied by a corresponding elevated immunoglobulin G antibody response to the novel Helicobacter sp. antigen. These data support other recent studies which demonstrate that multiple Helicobacter spp. in both naturally and experimentally infected mice can induce inflammatory bowel disease. The mouse model of helicobacter-associated intestinal inflammation should prove valuable in understanding how specific microbial antigens influence a complex disease process.
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PMID:A novel urease-negative Helicobacter species associated with colitis and typhlitis in IL-10-deficient mice. 1008 15

Most viral gene delivery syslems utilized to date have demonstrated significant limitations in practicality and safety due to the level and duration of recombinant transgene expression as well as their induction of host immunogenicity to vector proteins. Recombinant adeno-associated virus (rAAV) vectors appear to offer a vehicle for safe, long-term therapeutic gene transfer; factors afforded through the propensity of rAAV to establish long-term latency without deleterious effects on the host cell and the relative non-immunogenicity of the virus or viral expressed transgenes. The principal historical limitation of this vector system, efficiency of rAAV-mediated transduction, has recently observed a dramatic increase as the titer, purity, and production capacity of rAAV preparations have improved. In terms of systems that could benefit from such improvements, rAAV gene therapy to enhance solid organ transplantation would appear an obvious choice with islet transplantation forming a promising candidate due to the ability to perform viral transductions ex vivo. Currently, islet transplantation can be used to treat type 1 diabetes yet persisting alloimmune and autoimmune responses represent major obstacles to the clinical success for this procedure. The delivery of transgenes capable of interfering with antigenic recognition and/or cell death [e.g., Fas ligand (FasL), Bcl-2, Bcl-XL] as well as imparting tolerance/immunoregulation [e.g., interleukin(IL)-4, IL-10, transforming growth factor (TGF)-beta], or cytoprotection [e.g., heme oxygenase-1 (HO-1), catalase, manganese superoxide dismutase (MnSOD)] may prevent recurrent type 1 diabetes in islet transplantation and offer a promising form of immunotherapy. Research investigations utilizing such systems may also provide information vital to understanding the immunoregulatory mechanisms critical to the development of both alloimmune and autoimmune islet cell rejection mechanisms and recurrent type 1 diabetes.
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PMID:Adeno-associated virus (AAV) as a vehicle for therapeutic gene delivery: improvements in vector design and viral production enhance potential to prolong graft survival in pancreatic islet cell transplantation for the reversal of type 1 diabetes. 1189 74

A host's immune-defense system is suppressive by many factors in patients with cancer. We have previously shown one possible mechanism behind the T-cell dysfunction, whereby H(2)O(2) secreted from macrophages in tumor-draining lymph node (MTDL) induced T-cell dysfunction with down-regulation of TCR zeta molecules. In the present study, we analyzed how MTDL affect T cells, with a particular focus on T-cell apoptosis, by co-culturing MTDL with autologous peripheral blood T cells in gastric cancer. Moreover, we characterized the MTDL according to surface marker, oxygen-burst capacity and intracellular cytokine status. T-cell apoptosis was significantly induced in comparison to T-cell alone control in patients with advanced disease, concomitant to the elevated caspase activity and following impaired T-cell function. In patients with early disease, no significant difference was seen in the proportions of T cells that underwent apoptosis between T cells plus MTDL and T cells alone. Moreover, the addition of a selective scavenger of H(2)O(2), catalase inhibited the apoptosis of T cells co-cultured with MTDL in patients with advanced disease. In the characterization of MTDL, the production of H(2)O(2) in MTDL from advanced disease was significantly higher than that in early disease. The amounts of intracellular IL-10 and IL-12 in MTDL in advanced disease were significantly higher than those in early disease. These results indicated that MTDL induced apoptosis of autologous T cells and this T-cell dysfunction was mediated by H(2)O(2) derived from MTDL. Furthermore, the characteristics of MTDL including the capacity of oxygen-burst and intracellular cytokine production were different depending on the disease progression.
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PMID:Macrophages in tumor-draining lymph node with different characteristics induce T-cell apoptosis in patients with advanced stage-gastric cancer. 1258 34

The response of the fetal rat Type II pneumocyte (FTIIP), the stem cell of the alveolar epithelium, to hyperoxia would be helpful to understand the effects of oxygen-induced injury to the developing lung. Our goals were to evaluate the effect of antioxidants (AO) on apoptosis and release of cytokines in freshly isolated FTIIP (day-19) in the presence of 95% O2 and/or nitric oxide (NO). There was increased apoptosis in FTIIP exposed to hyperoxia alone and in combination with NO; this was significantly attenuated (p < 0.01) in the presence of 3 AO, namely grape seed proanthocyanidin extract (GSPE), superoxide dismutase (SOD) and catalase. The anti-inflammatory cytokine IL-10 has been shown to have a role in ameliorating tissue damage owing to persistent inflammation. The release of IL-10 was significantly decreased (p < 0.01) in the presence of GSPE and catalase, compared to control. Addition of SOD led to increased IL-10 compared to GSPE or catalase (p < 0.01) or the combination of GSPE + SOD + catalase (p < or = 0.01). Thus, in our in vitro model of hyperoxic and NO mediated injury to FTIIP, protection from apoptotic cell death with the addition of AO was associated with varying levels of IL-10 release. Our data suggest that the use of SOD and/or IL-10 may decrease hyperoxic lung injury by decreasing apoptosis. Further studies are needed to understand the mode of protection from catalase and GSPE.
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PMID:Effect of antioxidants on apoptosis and cytokine release in fetal rat Type II pneumocytes exposed to hyperoxia and nitric oxide. 1534 20

Whether methicillin-resistant Staphylococcus aureus (MRSA) constitutes per se an independent risk factor for morbidity and mortality after surgery as compared with methicillin-sensitive Staphylococcus aureus (MSSA) remains a subject of debate. The aim of this study was to assess whether innate defenses against MRSA and MSSA strains are similarly impaired after cardiac surgery. Both intracellular (isolated neutrophil functions) and extracellular (plasma) defenses of 12 patients undergoing scheduled cardiac surgery were evaluated preoperatively (day 0) and postoperatively (day 3) against two MSSA strains with a low level of catalase secretion and two MRSA strains with a high level of catalase secretion, inasmuch as SA killing by neutrophils relies on oxygen-dependent mechanisms. After surgery, an increase in plasma concentration of IL-10, an anti-inflammatory cytokine able to inhibit reactive oxygen species secretion and bactericidal activity of neutrophils, was evidenced. Despite the fact that univariate analysis suggested a specific impairment of neutrophil functions against MRSA strains, two-way repeated-measures ANOVA failed to demonstrate that the effect of S. aureus phenotype was significant. On the other hand, an increase in type-II secretory phospholipase A2 activity, a circulating enzyme involved in SA lysis, was evidenced and was associated with an enhancement of extracellular defenses (bactericidal activity of plasma) against MRSA. Overall, cardiac surgery and S. aureus phenotype had a significant effect on plasma bactericidal activity. Cardiac surgery was characterized by enhanced antibacterial defenses of plasma, whereas neutrophil killing properties were reduced. The overall effect of S. aureus phenotype on neutrophil functions did not seem significant.
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PMID:Blood neutrophil bactericidal activity against methicillin-resistant and methicillin-sensitive Staphylococcus aureus during cardiac surgery. 1604 79

The Brucella genus is able to cause chronic infection in a wide range of mammals including humans. Oxidative events, lipid peroxidation and inflammatory response against Brucella infection have not yet been well elucidated in vivo. We have investigated oxidative/antioxidative status and nitric oxide production in plasma, brain, liver and spleen during a 60 day period of B. melitensis infection in a rat model. In addition, inducible nitric oxide synthase (iNOS), IL-10, IL-12, IFN-gamma and TNF-alpha mRNA transcriptions were analyzed by semiquantitative reverse transcriptase PCR (RT-PCR) in brain samples. Animals were infected with B. melitensis and sacrificed at 7th, 15th, 30th, 45th and 60th day of post-inoculation. Malondialdehyde (MDA), as an indicator of lipid peroxidation, and nitric oxide (NO) concentrations were significantly increased after Brucella inoculation and began to decline to basal levels from 45th day in plasma, liver and spleen. However, iNOS transcription was not induced during the infection period in brains. In contrast, MDA level was increased in brain during the late phase of infection without any change in NO production. The infection did not alter the antioxidant enzyme activities in the tissues; although significantly increased catalase activity was observed between days 30 and 45 in the liver. Transcription analyses demonstrated that IL-10, IL-12 and IFN-gamma mRNA level were not induced in the brain. Only TNF-alpha mRNA was weakly up-regulated in brain 30 days after pathogen inoculation. The results obtained in this study demonstrate that B. melitensis induces lipid peroxidation and NO production in the liver and spleen in the early days of infection, but that these levels subsequently decline. Moreover, Brucella does not appear to induce antioxidant enzyme activities and inflammation during two months of infection. However, the pathogen does stimulate cerebral lipid peroxidation in the late phase of infection without causing significant inflammation.
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PMID:Evaluation of oxidative stress and inflammation in long term Brucella melitensis infection. 1681 May 61

Oxidative stress and inflammation are considered to be important factors in the pathogenesis of congestive heart failure subsequent to myocardial infarction. Endogenous TNF-alpha plays a central role in initiating and sustaining the inflammatory response. IL-10, an anti-inflammatory cytokine, has been shown to antagonize some of the deleterious effects of TNF-alpha. In this study, we tested whether an imbalance of these two contrasting cytokines leads to increased oxidative stress and cardiac myocyte dysfunction. Isolated adult rat cardiac myocytes were exposed to different concentrations of TNF-alpha and IL-10 (1-20 ng/ml) alone or in combination. As a positive control, cells were also exposed to H2O2 (100 microI) to induce oxidative stress. An exposure to TNF-alpha (10 ng/ml) caused a significant decrease in both protein and mRNA for manganese superoxide dismutase and catalase, decreased glutathione peroxidase protein, increased intracellular reactive oxygen species and lipid peroxidation, and caused cell injury as measured by creatine kinase release. IL-10 treatment (10 ng/ml) by itself had no effect on any of these parameters, but it prevented all the above listed changes caused by TNF-alpha. IL-10/TNF-alpha ratio of lower or higher than 1 was less effective in reducing TNF-alpha generated oxidative stress. H2O2 treatment increased oxidative stress and cell injury and TNF-alpha mimicked these effects. This study suggests that a proper balance between IL-10 and TNF-alpha, rather than any of the individual cytokines is of more physiological importance in mediating oxidative-stress-induced cardiac injury.
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PMID:Interplay of TNF-alpha and IL-10 in regulating oxidative stress in isolated adult cardiac myocytes. 1704 6


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