Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:P10145 (IL-8)
 23,849 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Cigarette smoking within minutes induces leukocyte adhesion to the vascular wall and formation of intravascular leukocyte-platelet aggregates. We find this is inhibited by platelet-activating factor (PAF) receptor antagonists, and correlates with the accumulation of PAF-like mediators in the blood of cigarette smoke-exposed hamsters. These mediators were PAF-like lipids, formed by nonenzymatic oxidative modification of existing phospholipids, that were distinct from biosynthetic PAF. These PAF-like lipids induced isolated human monocytes and platelets to aggregate, which greatly increased their secretion of IL-8 and macrophage inflammatory protein-1alpha. Both events were blocked by a PAF receptor antagonist. Similarly, blocking the PAF receptor in vivo blocked smoke-induced leukocyte aggregation and pavementing along the vascular wall. Dietary supplementation with the antioxidant vitamin C prevented the accumulation of PAF-like lipids, and it prevented cigarette smoke-induced leukocyte adhesion to the vascular wall and formation of leukocyte-platelet aggregates. This is the first in vivo demonstration of inflammatory phospholipid oxidation products and it suggests a molecular mechanism coupling cigarette smoke with rapid inflammatory changes. Inhibition of PAF-like lipid formation and their intravascular sequela by vitamin C suggests a simple dietary means to reduce smoking-related cardiovascular disease.
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PMID:Vitamin C blocks inflammatory platelet-activating factor mimetics created by cigarette smoking. 915 67

In order to contribute to the understanding of the biological properties of nafazatrom, an antithrombotic agent (NAP), we studied its effects on peroxidation of low density lipoproteins (LDL), lipid liposomes, heart homopgenate, and its interaction with alpha-tocopherol radical. NAP decreased the FeSO4 and H202-induced peroxidation of phosphatidylcholine liposomes and heart homogenate, and it decreased peroxidation of LDL induced by CuSO4 or 2,2'-azobis(2-amidinopropane). The antioxidant effect of NAF was about 3 times less potent than that of alpha-tocopherol (alpha-TOC) in phosphatidylcholine liposomes, and NAF was about 2-4 times more efficient to decrease peroxidation of LDL than alpha-TOC. Possible interaction of NAF with alpha-tocopherol radical (alpha-TR) was studied by EPR spectroscopy. NAF decreased the concentration of alpha-TR, but it was about 100-times less efficient than vitamin C. This may indicate that NAF does not interfere with alpha-TR formation and/or reduction of alpha-TR in biological system. The obtained results may help the explanation of biological effects of NAF.
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PMID:Nafazatrom inhibits peroxidation of phosphatidylcholine liposomes, heart homogenate and low density lipoproteins. 943 56

Long-term survival of lung transplant recipients is limited by the advent of obliterative bronchiolitis and irreversible airways obstruction, e.g. bronchiolitis obliterans syndrome (BOS). This study investigated whether inflammatory cells and their activation markers were increased in bronchoalveolar lavage (BAL) and transbronchial biopsies (TBB) from patients with BOS. Levels of antioxidants in BAL fluid were also assessed. BAL fluid and TBB from six single-lung, two bilateral-lung, and five heart-lung transplanted patients with diagnosis of BOS were compared with 13 transplant recipients without BOS. BAL fluid levels of myeloperoxidase (MPO), eosinophil cationic protein (ECP) and interleukin (IL)-8 were used as markers for the activation and attraction of neutrophils and eosinophils, respectively. Immunohistochemical staining of TBB with monoclonal antibodies to MPO and ECP (EG2) was performed. Significantly increased BAL percentages of neutrophils and levels of MPO were found in patients with BOS. The findings correlated well with the degree of monoclonal staining for MPO in TBB. BAL levels of ECP and IL-8 were significantly increased in BOS patients. BAL concentrations of the water-soluble antioxidants ascorbate, urate and glutathione were generally lower in BOS patients. The results indicate that neutrophil infiltration and activation, as well as oxidative stress, may play a role in the development and/or progression of bronchiolitis obliterans syndrome. Markers for neutrophil activation could have a potential role in monitoring disease activity in patients with this syndrome.
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PMID:Bronchiolitis obliterans syndrome in lung transplant recipients is associated with increased neutrophil activity and decreased antioxidant status in the lung. 970 19

The influence of vitamin C supplementation on the pattern of change in plasma cytokine concentrations was measured in 29 runners following a 90-km ultramarathon. The study was based on a 3 (groups) by 4 (blood samples at 16 prerace, postrace, and 24 h and 48 h postrace) repeated measures design. Groups included placebo control (n = 7) and two groups supplementing vitamin C at 500 mg/day (vit C-500, n = 10) or 1500 mg/day (vit C-1500, n = 12) for 7 days before the race, on race day, and for 2 days after the race. All measured plasma cytokine concentrations were significantly elevated immediately postrace, with the magnitude of increase for tumor necrosis factor-alpha (TNF-alpha) and interleukin-1beta (IL-1beta) much smaller than for IL-6, IL-10, IL-8, and IL-1 receptor antagonist (IL-1RA). Cortisol increased in all groups immediately after the race but significantly less in the vit C-1500 group. Group x time interaction statistics were not significant for any of the plasma cytokines. However, when the placebo and vit C-500 groups were combined (n = 17) and compared with the vit C-1500 group (n = 12), immediate postrace plasma concentrations were significantly lower in the vit C-1500 group for IL-1RA (-57%) and IL-10 (-57%), with a trend measured for IL-6 (-27%, p = 0.11) and IL-8 (-26%, p = 0.14). In summary, runners completing the 90-km Comrades Ultramarathon experienced strong increases in concentrations of plasma IL-6, IL-10, IL-1RA, and IL-8. These increases were attenuated in runners ingesting 1500 mg but not 500 mg vitamin C supplements for 1 week prior to the race and on race day.
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PMID:Influence of vitamin C supplementation on cytokine changes following an ultramarathon. 1109 61

The transcription factor NF-kappaB is a central mediator of altered gene expression during inflammation, and is implicated in a number of pathologies, including cancer, atherosclerosis, and viral infection. We report in this study that vitamin C inhibits the activation of NF-kappaB by multiple stimuli, including IL-1 and TNF in the endothelial cell line ECV304 and in primary HUVECs. The induction of a NF-kappaB-dependent gene, IL-8, by TNF was also inhibited. The effect requires millimolar concentrations of vitamin C, which occur intracellularly in vivo, particularly during inflammation. Vitamin C was not toxic to cells, did not inhibit another inducible transcription factor, STAT1, and had no effect on the DNA binding of NF-kappaB. Inhibition by vitamin C was not simply an antioxidant effect, because redox-insensitive pathways to NF-kappaB were also blocked. Vitamin C was shown to block IL-1- and TNF-mediated degradation and phosphorylation of I-kappaBalpha (inhibitory protein that dissociates from NF-kappaB), due to inhibition of I-kappaB kinase (IKK) activation. Inhibition of TNF-driven IKK activation was mediated by p38 mitogen-activated protein kinase, because treatment of cells with vitamin C led to a rapid and sustained activation of p38, and the specific p38 inhibitor SB203580 reversed the inhibitory effect of vitamin C on IKK activity, I-kappaBalpha phosphorylation, and NF-kappaB activation. The results identify p38 as an intracellular target for high dose vitamin C.
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PMID:Vitamin C inhibits NF-kappa B activation by TNF via the activation of p38 mitogen-activated protein kinase. 1112 Aug 50

The purpose of this randomized study was to measure the influence of vitamin C (n = 15 runners) compared with placebo (n = 13 runners) supplementation on oxidative and immune changes in runners competing in an ultramarathon race. During the 7-day period before the race and on race day, subjects ingested in randomized, double-blind fashion 1,500 mg/day vitamin C or placebo. On race day, blood samples were collected 1 h before race, after 32 km of running, and then again immediately after race. Subjects in both groups maintained an intensity of approximately 75% maximal heart rate throughout the ultramarathon race and ran a mean of 69 km (range: 48-80 km) in 9.8 h (range: 5-12 h). Plasma ascorbic acid was markedly higher in the vitamin C compared with placebo group prerace and rose more strongly in the vitamin C group during the race (postrace: 3.21 +/- 0.29 and 1.28 +/- 0.12 microg/100 microl, respectively, P < 0.001). No significant group or interaction effects were measured for lipid hydroperoxide, F2-isoprostane, immune cell counts, plasma interleukin (IL)-6, IL-10, IL-1-receptor antagonist, or IL-8 concentrations, or mitogen-stimulated lymphocyte proliferation and IL-2 and IFN-gamma production. These data indicate that vitamin C supplementation in carbohydrate-fed runners does not serve as a countermeasure to oxidative and immune changes during or after a competitive ultramarathon race.
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PMID:Influence of vitamin C supplementation on oxidative and immune changes after an ultramarathon. 1196 Sep 47

Periodontal disease is a common chronic adult condition. The bacterium Porphyromonas gingivalis has been implicated in the aetiology of this disease, which causes destruction of the connective tissue and bone around the root area of the tooth. It has been observed that invading P. gingivalis bacteria trigger the release of cytokines such as interleukin 8 and tumour necrosis factor a, leading to elevated numbers and activity of polymorphonucleocytes (PMN). As a result of stimulation by bacterial antigens, PMN produce the reactive oxygen species (ROS) superoxide via the respiratory burst as part of the host response to infection. Patients with periodontal disease display increased PMN number and activity. It has been suggested that this proliferation results in a high degree of ROS release, culminating in heightened oxidative damage to gingival tissue, periodontal ligament and alveolar bone. Antioxidant constituents in plasma have been well-documented, being chiefly ascorbate, albumin and urate, and these are known to display sensitivity to dietary antioxidant intakes. The concentration of antioxidants in saliva does not appear to mirror those of plasma. The extent of dietary influence upon salivary antioxidant status is unclear. Urate is the predominant salivary antioxidant, with albumin and ascorbate providing minor contributions. Previous research has found reduced salivary antioxidant activity in patients suffering from periodontal disease. An improved understanding of the role antioxidants play in periodontitis, and the influence of nutrition on antioxidant status, may lead to a possible nutritional strategy for the treatment of periodontal disease.
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PMID:Salivary antioxidants and periodontal disease status. 1200 88

To characterize the role of intestinal epithelial cells in mucosal host defense, we have examined endogenous antioxidant reactivity and inflammatory response in Caco-2 cell line. When differentiated Caco-2 cells were incubated with iron/ascorbate for 1-24 h, they exhibited increased malondialdehyde levels and decreased polyunsaturated fatty acid proportion in favor of saturated fatty acids. These modifications were accompanied with alterations in membrane fluidity and permeability. The oxidative stress did not induce changes in the antioxidant enzyme activity of superoxide dismutase, catalase, glutathione peroxidase, and glutathione transferase, or in cellular glutathione content. However, iron/ascorbate-mediated lipid peroxidation promoted inhibitor-kappaB degradation and NF-kappaB activation, as well as gave rise to IL-8, cyclooxygenase-2, and ICAM-1. These results support the importance of oxidant/antioxidant balance in the epithelial cell inflammatory response.
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PMID:Inflammatory reaction without endogenous antioxidant response in Caco-2 cells exposed to iron/ascorbate-mediated lipid peroxidation. 1284 21

The inflammatory response to ozone in atopic asthma suggests that soluble mediators of inflammation are released in response to oxidant stress. Antioxidants may alleviate additional oxidative stress associated with photochemical oxidant pollution. This study investigates the impact of antioxidant supplementation on the nasal inflammatory response to ozone exposure in atopic asthmatic children. We conducted a randomized trial using a double-blinded design. Children with asthma (n = 117), residents of Mexico City, were given randomly a daily supplement of vitamins (50 mg/day of vitamin E and 250 mg/day of vitamin C) or placebo. Nasal lavages were performed three times during the 4-month follow-up and analysed for content of interleukin-6 (IL-6), IL-8, uric acid and glutathione (GSx). IL-6 levels in the nasal lavage were increased significantly in the placebo group after ozone exposure while no increase was observed in the supplement group. The difference in response to ozone exposure between the two groups was significant (P = 0.02). Results were similar for IL-8, but with no significant difference between the groups (P = 0.12). GSx decreased significantly in both groups. Uric acid decreased slightly in the placebo group. Our data suggest that vitamin C and E supplementation above the minimum dietary requirement in asthmatic children with a low intake of vitamin E might provide some protection against the nasal acute inflammatory response to ozone.
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PMID:Antioxidant supplementation and nasal inflammatory responses among young asthmatics exposed to high levels of ozone. 1549 43

Oxidative stress seems to contribute to cardiopulmonary bypass (CPB)-related postoperative complications. Pediatric patients are particularly prone to these complications. With this in mind, we measured oxidative stress markers in blood plasma of 20 children undergoing elective heart surgery before, during, and up to 48 h after cessation of CPB, along with inflammatory parameters and full analysis of iron status. Ascorbate levels were decreased by approximately 50% (P < 0.001) at the time of aorta cross-clamp removal (or pump switch-off in 4 patients with partial CPB), and associated with corresponding increases in dehydroascorbate (P < 0.001, r = -0.80) and malondialdehyde (P < 0.01, r = -0.59). In contrast to the immediate oxidative response, peak levels of IL-6 and IL-8 were not observed until 3-12 h after CPB cessation. The early loss of ascorbate correlated with duration of CPB (P < 0.002, r = 0.72), plasma hemoglobin after cross-clamp removal (P < 0.001, r = 0.70), and IL-6 and IL-8 levels at 24 and 48 h after CPB (P < 0.01), but not with postoperative lactate levels, strongly suggesting that hemolysis, and not inflammation or ischemia, was the main cause of early oxidative stress. The correlation of ventilation time with early changes in ascorbate (P < 0.02, r = 0.55), plasma hemoglobin (P < 0.01, r = 0.60), and malondialdehyde (P < 0.02, r = 0.54) suggests that hemolysis-induced oxidative stress may be an underlying cause of CPB-associated pulmonary dysfunction. Optimization of surgical procedures or therapeutic intervention that minimize hemolysis (e.g., off-pump surgery) or the resultant oxidative stress (e.g., antioxidant treatment) should be considered as possible strategies to lower the rate of postoperative complications in pediatric CPB.
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PMID:Oxidative stress precedes peak systemic inflammatory response in pediatric patients undergoing cardiopulmonary bypass operation. 1585 50


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