Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:3.4.21.37 (neutrophil elastase)
 4,078 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Amniotic fluid was obtained from 180 patients by amniocentesis at 16-22 weeks of gestation and assayed for the levels of interleukin (IL)-6, IL-8, leukocyte elastase (LE), and glucose. Ten of cases had clinical symptoms, such as uterine contraction, genital bleeding, and cervical ripening, and the other 170 were assessed for fetal chromosomal features. Four of the ten cases with uterine contraction developed abortion, while 10 of those screened had findings of fetal chromosomal anomalies, and 7 cases then underwent induced abortion artificially. In the cases of abortion, levels of IL-6, IL-8 and LE were higher than in the samples from the 160 pregnant women without clinical symptoms and a normal karyotype, while glucose in amniotic fluid was lower. Of 6 cases with clinical symptoms, but not developing abortion, 4 developed preterm labor, and in these IL-6 and IL-8 also were significantly elevated, with LE being slight high compared to normal. The results suggest that IL-6, IL-8, LE, and glucose in amniotic fluid at early second trimester can be used as markers of severe infection in the uterus, and with the first two being particularly sensitive.
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PMID:Evaluation levels of cytokines in amniotic fluid of women with intrauterine infection in the early second trimester. 1635 74

We investigated the effects of antithrombin on coagulation, fibrinolysis, and production of cytokines and adhesion molecules in abdominal aortic aneurysm repair surgery. Sixteen patients for Y-shaped graft replacement of abdominal aortic aneurysm were divided into an antithrombin group and a control group. In the antithrombin group, 3000 U antithrombin was infused over 30 min before heparin administration and 24 h later. White blood cell counts, platelet counts, prothrombin time ratio, and serum concentrations of antithrombin, polymorphonuclear leukocyte elastase, interleukin (IL)-1beta, IL-6, IL-8, tumor necrosis factor-alpha, and adhesion molecules, and variables of coagulation and fibrinolysis were measured before surgery, at the end of surgery, and 1 and 2 days after surgery. The antithrombin concentration decreased in the control group, whereas it increased in the antithrombin group with significant differences between the groups. Prothrombin time ratio, concentrations of d-dimer, thrombin-antithrombin complex, and intercellular adhesion molecule-1 increased only in the control group and polymorphonuclear leukocyte elastase, IL-6, tumor necrosis factor-alpha, and vascular cell adhesion molecule-1 increased in both groups. They were significantly less in the antithrombin group except for intercellular adhesion molecule-1. In conclusion, antithrombin could decrease hypercoagulation and inflammatory activation during abdominal aortic aneurysm surgery, which may decrease adverse events.
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PMID:Antithrombin can modulate coagulation, cytokine production, and expression of adhesion molecules in abdominal aortic aneurysm repair surgery. 1655 89

Oxygen radicals have recently been attracting close attention because of their involvement in tissue damage and their close relationship to various clinical conditions. It has been suggested that hemodialysis increases oxidative stress, triggering the development of complications such as atherosclerosis and dialysis-related amyloidosis. We recently developed a dialyzer containing a highly functional polysulfone membrane on which vitamin E had been bonded (PS-ViE). The present study was undertaken to evaluate the biocompatibility of this membrane and to conduct other experiments on the membrane in vitro. Human blood was dialyzed with minidialyzers (300-600 cm(2) membrane area) made of PS-ViE, cellulose, or untreated polusulfone (PS), and the effects of the dialyzers on complements (C3a, C4a, and C5a), cytokines (IL-1beta and IL-8), and granulocyte elastase as well as their anti-oxidative activity were investigated (n = 6). The effect of PS-ViE on complement activation and its effects on cytokines were comparable to those of PS membrane, whereas granulocyte elastase following dialysis with the PS-ViE membrane tended to be lower than that seen with PS membrane. The effects of PS-ViE-induced methemoglobin, lipid peroxide, and oxygen radicals were significantly less than those of PS membrane, indicating the antioxidative activity of PS-ViE. Vitamin E-modified polysulfone membrane dialyzers were found to have favorable effects on the immune system and to express antithrombotic and antioxidative effects.
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PMID:Development of vitamin E-modified polysulfone membrane dialyzers. 1661 2

In this study, we investigated the regulation and mechanism of IL-8 expression by A549 human lung carcinoma cells treated with neutrophil elastase (NE). NE-treated cells exhibited significantly higher IL-8 protein levels in culture media compared with cells treated with vehicle alone. Blocking of gene transcription with actinomycin D suggested that NE stimulated IL-8 synthesis via increased mRNA expression, which was verified by real-time RT-PCR. NE activated the IL-8 promoter but did not alter the stability of its mRNA, confirming that the protease induced IL-8 synthesis through increased gene transcription. The results from the use of chemical inhibitors and mutant gene constructs against various signal transduction components seem to suggest the linear signaling pathway involving the activation of PKC-delta --> dual oxidase 1 --> reactive oxygen species --> TNF-alpha-converting enzyme --> EGF receptor --> p38 --> NF-kappaB for NE-activated IL-8 gene expression. A NF-kappaB potential binding site, located between nucleotides -82 and -69 of the IL-8 promoter, was identified as necessary for NE-induced IL-8 transcription. We conclude that NE increases IL-8 transcription through p38/NF-kappaB activation via EGFR transactivation.
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PMID:Neutrophil elastase induces IL-8 gene transcription and protein release through p38/NF-{kappa}B activation via EGFR transactivation in a lung epithelial cell line. 1663 17

We examined whether epithelial damage is associated with mobilization of neutrophils or eosinophils in the airway lumen during acute exacerbations of paediatric asthma. Aspirated sputum samples were harvested from 65 paediatric patients (mean age 3.4 +/- 0.4 years) during acute exacerbations of asthma. Patients with signs of infection were excluded. The presence of conglomerates of epithelial cells (i.e. "Creola bodies") in the aspirated sputum was utilized as a marker of epithelial damage. Among the paediatric asthma patients, 60% displayed Creola bodies (CrB+: n = 39) in their sputum samples whereas the remaining patients did not (CrB-: n = 26). CrB+ patients displayed more than a 20-fold increase in the concentration of the neutrophil-mobilizing cytokine interleukin (IL)-8 (pg/ml) and of the neutrophil product neutrophil elastase (NE, g/l), respectively, compared with CrB- patients (IL-8: 7468.2 +/- 1953.6 versus 347.9 +/- 72.6, P < 0.01; NE: 2072.4 +/- 419.0 versus 438.5 +/- 125.7, P < 0.01). Even though not statistically significant, a corresponding trend was observed for the relative number of sputum neutrophils. In contrast, the concentration of the eosinophil-mobilizing cytokine IL-5 and the esoinophil product ECP tended to be lower in CrB+ than in CrB- patients (P > 0.05). In conclusion, as indicated by the analysis of aspirated sputum, epithelial damage is associated with a locally enhanced chemotactic signal for and activity of neutrophils, but not eosinophils, during acute exacerbations of paediatric asthma. It remains to be determined whether these indirect signs of neutrophil mobilization in the airway lumen mirror an increased number of neutrophils in the surrounding airway tissue.
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PMID:Association of epithelial damage and signs of neutrophil mobilization in the airways during acute exacerbations of paediatric asthma. 1663 93

Myeloid-related protein-8 (MRP-8), MRP-14, and MRP-8/14 are found in a variety of inflammatory conditions and are involved in the host defense system. The objective of this study was to determine the concentrations of MRP-8, MRP-14, and MRP-8/14 in human cervical mucus and the associations between MRP-8/14 and proinflammatory cytokines. Samples of cervical mucus were obtained using a syringe from sexually active women (n=97) during the preovulatory phase. Samples from seven women were obtained using a swab placed in the cervical canal during the proliferative, preovulatory, and luteal phases. Concentrations of MRP-8, MRP-14, MRP-8/14, IL-1alpha, IL-6, IL-8, and granulocyte elastase were measured using an ELISA. The mean levels of MRP-8, MRP-14, and MRP-8/14 in cervical mucus were 1.87, 0.46, and 23.90microg/ml, respectively. The concentration of MRP-8/14 showed positive correlations with concentrations of IL-1alpha (p<0.0001), IL-8 (p<0.0001), and granulocyte elastase (p<0.0001). However, there were no significant differences in MRP-8/14 levels in the cervical mucus of each patient during the menstrual cycle. MRP-8/14 was mainly detected in human cervical mucus and showed a positive correlation with proinflammatory cytokines. The MRP-8/14 level in cervical mucus may be useful as a marker of inflammation of the uterine cervix.
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PMID:Myeloid-related protein-8/14 is associated with proinflammatory cytokines in cervical mucus. 1680 87

Lactoferrin (Lf) is a member of the transferrin family of iron-binding anti-bacterial proteins, present in most exocrine secretions, such as saliva, and plays an important role in mucosal defense. In this study, we identified small Lf peptides with Con A low-affinity in the parotid saliva of chronic periodontitis patients by Con A two-dimensional immunoelectrophoresis, Con A affinity chromatography and Western blotting using anti-human Lf polyclonal Ab. N-terminal amino acid sequencing of the four Con A low-affinity Lf peptides confirmed them to be fragments of intact Lf. The detection ratio of the proteinase 3 (PR3)-like activity was elevated in the parotid saliva of periodontitis patients and was associated with the severity of clinical symptoms. PR3 protein was also detected in the parotid saliva of periodontitis patients, and PR3, but not human leukocyte elastase and cathepsin G, degraded intact Lf. Con A low-affinity saliva Lf peptides showed no anti-bacterial activity against Escherichia coli, and had a reduced iron-chelating capacity. Con A low-affinity saliva Lf peptides, PR3-treated Lf preparation and two of four synthetic polypeptides induced the production of interleukin IL-6, monocyte chemoattractant protein-1 and IL-8, and the activation of NF-kappaB in human oral epithelial HSC-2 cells. Furthermore, concentrations of the Lf peptides in the parotid saliva of periodontitis patients were increased with a correlation to the severity of clinical symptoms. These results suggest that Lf in the parotid saliva of periodontitis patients was degraded into small peptides by the PR3-like activity with the capability to induce inflammatory mediators.
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PMID:Cleaved inflammatory lactoferrin peptides in parotid saliva of periodontitis patients. 1703 Mar 85

Cardiopulmonary bypass (CPB) is believed to cause postoperative lung dysfunction. To more closely examine the inflammatory processes occurring in the airways during CPB, we serially measured inflammatory mediators, with the assistance of a new bronchoscopic microsample probe, in 11 patients undergoing repair of aortic arch aneurysms. Epithelial lining fluid (ELF) and arterial blood were sampled simultaneously after induction of anesthesia, at the time of pulmonary reperfusion, and at the end of surgery. A decrease in the PaO2/FiO2 ratio was observed at the end of surgery (P = 0.029). Although the ELF concentrations of interleukin (IL)-8, IL-6, and neutrophil elastase had increased significantly at the end of surgery (median = 23,200, 1818, and 12,900 microg/mL, respectively), they did not correlate with the degree of hypoxemia. Neutrophil elastase increased significantly at the time of pulmonary reperfusion, before IL-8 and IL-6, and independently of blood transfusions. At the end of surgery, IL-6 in ELF correlated with total blood transfusion volume (rho = 0.731, P = 0.011). These results indicate that a neutrophil-derived inflammatory response is activated in the airway in the early phase of CPB.
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PMID:Activation of a neutrophil-derived inflammatory response in the airways during cardiopulmonary bypass. 1712 9

Elafin (or skin-derived antileukoprotease) and secretory leukocyte protease inhibitor (SLPI) are serine antiproteases antagonizing human neutrophil elastase (HNE), thereby preventing tissue injury from excessive release of proteolytic enzymes by inflammatory cells. Furthermore, elafin and SLPI are "defensin-like" molecules with broad antimicrobial activity. The balance between proteases and antagonists may critically determine inflammatory processes in Crohn's disease (CD) and ulcerative colitis (UC). Real-time PCR was performed to quantitate colonic, proinflammatory cytokine IL-8, protease (HNE), and antiprotease mRNA (elafin and SLPI) in a total of 340 biopsies from 117 patients (47 CD, 45 UC, 25 controls). Histological inflammation was scored, and HNE, elafin, and SLPI were localized and semiquantified by immunostaining in 51 colonic paraffin sections (23 CD, 11 UC, 17 controls). Proinflammatory IL-8, degree of histological inflammation, and granulocyte content were similar in UC and CD. Elafin stained predominantly in the epithelium and SLPI in mucosal inflammatory cells. HNE mRNA levels and immunostaining were increased equally in both forms of inflammatory bowel disease. Levels of mRNA and immunostaining of the antiproteases elafin and SLPI were enhanced strongly in inflamed versus noninflamed UC. It is surprising that comparing inflamed versus noninflamed CD, this increase was significantly less pronounced for elafin and even lacking for SLPI. Despite comparable degrees of inflammation and protease levels, the induction of both antiproteases was attenuated in CD. This could contribute to the transmural depth of tissue destruction in CD. Elafin and SLPI may be added to the list of defensin-like peptides with diminished induction in CD versus UC.
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PMID:Attenuated induction of epithelial and leukocyte serine antiproteases elafin and secretory leukocyte protease inhibitor in Crohn's disease. 1720 Jan 45

The minimal cardiopulmonary bypass (mini-CPB) circuit, a closed system with neither cardiotomy suction nor an open venous reservoir and thus no air-blood interface, reportedly reduces blood loss and inflammatory reactions associated with coronary bypass surgery. We evaluated the inflammatory reactions in patients in whom coronary bypass operations were performed with conventional CPB or mini-CPB (n=15 each). Interleukin (IL)-6, IL-8, and neutrophil elastase levels; the neutrophil count; and the C-reactive protein value were measured before and immediately after surgery and on postoperative days 1 and 2. In addition, intraoperative blood loss and the transfusion volume were evaluated in these groups. Neutrophil elastase levels were lower in the mini-CPB group than in the conventional group on postoperative days 1 (127 +/- 52 vs. 240 +/- 100 microg/l, P=0.013) and 2 (107 +/- 17 vs. 170 +/- 45 micro/l, P=0.0001), as was the IL-8 level on postoperative day 1 (8.3 +/- 6.4 vs. 19 +/- 11 pg/ml, P=0.016). The intraoperative blood loss and transfusion volumes were significantly lower in the mini-CPB group than in the conventional group (510 +/- 244 vs. 1046 +/- 966 ml, P=0.012, and 691 +/- 427 vs. 1416 +/- 918 ml, P=0.0033). Thus, mini-CPB appears to attenuate neutrophil activation and cytokine release after coronary bypass surgery and, in addition, has some beneficial effects on blood conservation.
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PMID:Minimal cardiopulmonary bypass attenuates neutrophil activation and cytokine release in coronary artery bypass grafting. 1757 11


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