Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:P05231 (interleukin-6)
 23,907 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Vascular endothelium produces and/or interferes with various cytokines. Previous studies have demonstrated interactions of these inflammatory and immunological mediators with oxygen-derived free radicals. The present work examines the relationship between hypoxia/reoxygenation (H/R) and cytokine production by cultured endothelial cells. Human umbilical vein endothelial cell (HUVEC) monolayers were incubated for 24 h in normoxia or submitted to 5 h hypoxia/19 h reoxygenation. Then, interleukin-1 (IL-1) alpha and beta, and interleukin-6 (IL-6), were measured in culture supernatants by specific enzyme immunoassays and bioassays, respectively. Under these conditions, the spontaneous production of IL-1 and IL-6, detected in normoxic HUVEC, greatly increased after H/R treatment. The observed enhancement was cycloheximide-sensitive and, consequently, reflected a de novo protein synthesis. Superoxide dismutase and glutathione peroxidase prevented H/R-induced IL-1 and IL-6 increase. These results constitute the first demonstration that H/R stimulates HUVEC to promote IL-1 and IL-6 production and strongly suggest a role for oxygen-derived free radicals in the cytokine synthesis.
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PMID:Hypoxia/reoxygenation stimulates endothelial cells to promote interleukin-1 and interleukin-6 production. Effects of free radical scavengers. 145 74

We have investigated the effect of transforming growth factor-beta 1 (TGF-beta 1) and three cytokines on expression of antioxidative enzymes, manganese-superoxide dismutase, copper, zinc-superoxide dismutase, and catalase in cultured hepatocytes of rat. While interleukin-1 beta and interleukin-6 induced manganese-superoxide dismutase gene expression, they slightly suppressed catalase gene expression in rat hepatocytes. TGF-beta 1 suppressed expression of all these antioxidative enzymes in time- and cell density-dependent manners. Furthermore, we examined the effect of TGF-beta 1 on expression of glutathione peroxidase and glutathione-S-transferase, which exhibit glutathione-dependent peroxidase activity in rat hepatocytes. Expression of two major classes of the rat glutathione-S-transferase subunits 1 and 2 was also reduced by TGF-beta 1, although expression of glutathione peroxidase was not affected. Flow cytometric analysis indicated that production of peroxides was increased in hepatocytes treated with TGF-beta 1. These data suggest that augmented production of hydrogen peroxide and its intermediate through suppression of antioxidative enzyme expression may participate in cellular injury or growth inhibition promoted by TGF-beta 1.
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PMID:Suppression of antioxidative enzyme expression by transforming growth factor-beta 1 in rat hepatocytes. 751 58

Nuclear factor kappa B (NF-kappa B) is a potent and pleiotropic transcription factor that can be activated by a wide variety of inducers, including interleukin-1 (IL-1). Although the detailed activation mechanism of NF-kappa B is still under investigation, it requires both phosphorylation and degradation of its inhibitory subunit I kappa B and the presence of an oxidative environment. In this study, we systematically evaluated the influence of glutathione peroxidase, glutathione reductase and catalase on IL-1-induced NF-kappa B activation by analysing the effect of specific inhibitors of these enzymes. For the three antioxidant enzymes mentioned, their inhibition correlated with an overactivation of NF-kappa B, particularly for glutathione peroxidase. Inversely, we tested the response of glutathione peroxidase-transfected cells on NF-kappa B activation, which was lower as compared with the parental cells. Furthermore, interleukin-6 production also correlated perfectly with the reduced level of NF-kappa B activation is these experiments. The results clearly show that NF-kappa B activation is, strongly dependent on the antioxidant potential of the cells, especially on the activity of reduced glutathione-dependent enzymes such as glutathione peroxidase. The results support the hypothesis that the level of the oxidised glutathione:reduced glutathione ratio and the activity of intracellular antioxidant enzymes play a major role in NF-kappa B tine tuning.
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PMID:Effects of antioxidant enzyme modulations on interleukin-1-induced nuclear factor kappa B activation. 903 47

This study was aimed at an assessment of the role of oxygen-derived free radicals, cytokines and endogenous cholecystokinin (CCK) in the pathogenesis of L-arginine (Arg)-induced acute pancreatitis in rat. We measured the levels of malonyl dialdehyde (MDA), glutathione peroxidase (GPx), catalase and superoxide dismutase (Mn- and Cu, Zn-SOD) in pancreatic tissue, the serum levels of tumor necrosis factor-alpha (TNF-alpha), interleukin-6 (IL-6) and CCK, and evaluated the protective effect of the xanthine oxidase inhibitor allopurinol and a novel CCK receptor antagonist KSG-504. Acute pancreatitis was induced in male Wistar rats by injecting 2x 250 mg/100 g body weight of Arg intraperitoneally in an 1-h interval, as a 20% solution in 0.15 M NaCl. Control rats received the same quantity of glycine. 200 mg x kg(-1) allopurinol 30 min before the first Arg treatment or 50 mg x kg(-1) KSG-504 30 min before and 6, 18 and 36 h after the first Arg injection was administered subcutaneously. Rats were killed at 6, 12, 24 and 48 h following Arg administration, and acute pancreatitis was confirmed by a serum amylase level elevation and typical inflammatory features observed microscopically. The serum level of amylase reached the peak level at 24 h after the Arg injection (30,800 +/- 3,813 versus 6,382 +/- 184 U x L(-1) in the control) and normalized at 48 h. The tissue concentration of MDA was significantly elevated at 24 h, and reached the peak value at 48 h (5.00 +/- 1.75 versus 0.28 +/- 0.05 nM x mg(-1) protein in the control). The catalase and Mn-SOD activities were significantly decreased throughout the study, while the GPx activity was significantly reduced at 6 and 12 h, and the Cu, Zn-SOD activity was significantly lower at 12 h after the Arg injection as compared with the controls. Both the TNF-alpha and the IL-6 levels were already elevated significantly at 12 h and peak at 24 h versus the controls (19.1 +/- 7.9 U x mL(-1) and 57.6 +/- 11.2 pg x mL(-1) versus 3.1 +/- 0.8 U x mL(-1) and 15.2 +/- 3.1 pg x mL(-1), respectively). No significant changes in plasma CCK levels were observed. Allopurinol treatment markedly reduced the serum amylase elevation (12.631 +/- 2.257 U x L(-1) at 24 h), prevented the increase in tissue MDA concentration (0.55 +/- 0.09 nM x mg(-1) protein at 48 h) and significantly ameliorated the pancreatic edema, necrosis and inflammation at 48 h after Arg administration. KSG-504 administration did not exert any beneficial effect on the development of histopathological changes neither modified the serum amylase or cytokine levels. Oxygen-derived free radicals and cytokines are involved, while endogenous CCK does not seem to play a role in the pathogenesis of Arg-induced acute pancreatitis.
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PMID:The pathogenesis of L-arginine-induced acute necrotizing pancreatitis: inflammatory mediators and endogenous cholecystokinin. 1076 88

To evaluate the early molecular events of oxidant-induced pulmonary fibrosis, rats were continuously exposed to 0.4 ppm ozone and 7 ppm nitrogen dioxide. The early responses to the combined gases could be divided into three phases. Acute pulmonary inflammation indicated by an increase in pulmonary edema as well as an influx of neutrophils into the airspaces first occurred on days 1 to 3 of the exposure. The pulmonary inflammation was reversed by day 8, and no biochemical or morphologic aspects of tissue responses were detected from days 15 to 45, suggesting that rats adapted to the stimuli during that period. Pulmonary fibrosis could be detected by an increase in the biomarker of lung collagen content at day 60 and by histopathologic evaluation by day 90. Enhanced expression of macrophage inflammatory protein-2 was observed only at day 1, whereas the pulmonary expression of transforming growth factor-beta was upregulated on days 60 and 90 of the exposure. Macrophage expressions of interleukin-1beta and interleukin-6 were enhanced during acute pulmonary inflammation; however, macrophage expression of tumor necrosis factor-alpha was elevated at both day 1 and days 60-90. Activation of nuclear factor-kappa B and increased expression of thioredoxin in the lungs was also observed at day 1 and days 60-90. The expression of antioxidant enzymes, such as manganeous superoxide dismutase and glutathione peroxidase, was not altered during exposure. These results indicate that macrophage activation and the expression of macrophage-derived cytokines may play an important role in the early pulmonary responses against the combined gases.
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PMID:Early molecular and cellular events of oxidant-induced pulmonary fibrosis in rats. 1098 8

The generation of reactive oxygen species (free radicals) is an important factor in the development and maintenance of rheumatoid arthritis in humans and animal models. One source of free radicals is nitric oxide produced within the synoviocytes and chondrocytes and giving rise to the highly toxic radical peroxynitrite. Several cytokines, including tumour necrosis factor-alpha (TNFalpha) are involved in the formation of free radicals, partly by increasing the activity of nitric oxide synthase. Indeed, nitric oxide may mediate some of the deleterious effects of cytokines on bone resorption. Aspirin, tetracyclines, steroids and methotrexate can suppress nitric oxide synthase. Dietary antioxidants include ascorbate and the tocopherols and beneficial effects of high doses have been reported especially in osteoarthritis. There is also evidence for beneficial effects of beta-carotene and selenium, the latter being a component of the antioxidant enzyme glutathione peroxidase. The polyunsaturated fatty acids (PUFA) include the n-3 compounds, some of which are precursors of eicosanoid synthesis, and the n-6 group which can increase formation of the pro-inflammatory cytokines TNFalpha and interleukin-6, and of reactive oxygen species. Some prostaglandins, however, suppress cytokine formation, so that n-3 PUFA often oppose the inflammatory effects of some n-6-PUFA. gamma-linolenic acid (GLA) is a precursor of prostaglandin E1, a fact which may account for its reported ability to ameliorate arthritic symptoms. Fish oil supplements, rich in n-3 PUFA such as eicosapentaenoic acid have been claimed as beneficial in rheumatoid arthritis, possibly by suppression of the immune system and its cytokine repertoire. Some other oils of marine origin (e.g. from the green-lipped mussel) and a range of vegetable oils (e.g. olive oil and evening primrose oil) have indirect anti-inflammatory actions, probably mediated via prostaglandin E1. Overall, there is a growing scientific rationale for the use of dietary supplements as adjuncts in the treatment of inflammatory disorders such as rheumatoid arthritis and osteoarthritis.
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PMID:Antioxidants and fatty acids in the amelioration of rheumatoid arthritis and related disorders. 1129 72

This study was designed to investigate the effects of pre-infusion with total parenteral nutrition (TPN) using medium-chain triglyceride (MCT) versus long-chain triglyceride (LCT) emulsion as fat sources on hepatic lipids, inflammatory mediators and antioxidant capacity in rats undergoing gastrectomy. Rats with internal jugular catheter, were divided into two groups and received TPN. TPN supplied 300 kcal/kg/d with 39% of the energy provided as fat. All TPN solutions were isonitrogenous and identical in nutrient composition except for the fat emulsion, which was composed of MCT/LCT (1 : 1) or LCT. After receiving TPN for 5 days, the rats underwent partial gastrectomy and were sacrificed 24 h after surgery. The results of the study demonstrated that the MCL/LCT group had lower hepatic lipids than did the LCT group. No differences in interleukin-1beta, interleukin-6 and tumor necrosis factor-alpha in peritoneal lavage fluid were observed between the two groups. Erythrocyte glutathione peroxidase activity was significantly higher in the LCT group than the MCT/LCT group, although erythrocyte superoxide dismutase activity did not differ significantly between the two groups. These results suggest that infusion with MCT/LCT before an abdominal operation did not have an effect on modulating the production of inflammatory mediators in the location of the injurious stimulus. However, pre-infusion with MCT/LCT have beneficial effect in improving liver lipid metabolism and reducing oxidative stress in rats with gastrectomy.
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PMID:Effects of medium-chain triglyceride in parenteral nutrition on rats undergoing gastrectomy. 1188 11

The aim of this study was to examine solvent-associated effects on blood cytokine levels, antioxidant enzyme activities, and malondialdehyde (MDA) concentration in house painters. Trace element (Cu and Zn) and nitrite and nitrate levels as well as protein concentrations in erythrocytes and serum were determined. Thirty male house painters and 30 male clerical workers were included in the study. There were 13 smokers and 17 nonsmokers in each group. Hemoglobin concentrations were significantly lower in house-painter blood compared to controls. House painters had significantly higher concentrations of erythrocyte protein (excluding hemoglobin), whereas no significant difference was observed between serum protein levels. Proinflammatory cytokine levels, such as tumor necrosis factor-alpha and interleukin-8, were significantly increased in house painters' sera. Interleukin-6 was below the detection limit of the assay in both groups. Interleukin-1beta and cytokine receptor interleukin 2R concentrations were not significantly affected. Furthermore, a three- to fourfold increase in nitrite and nitrate concentrations was found in house painters' sera. Serum superoxide dismutase (SOD) and glutathione peroxidase (GSHPx) activities were significantly lower in house painters compared to controls. Malondialdehyde (MDA) concentration, a measure of lipid peroxidation, was found to be significantly elevated. In house painters, erythrocyte carbonic anhydrase and catalase activities were elevated approximately 11- fold and 2-fold, respectively. Zinc levels were significantly decreased in house painters' sera. Smoking was not found to be a major confounder for the association between solvent exposure and blood parameters.
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PMID:Effects of long-term solvent exposure on blood cytokine levels and antioxidant enzyme activities in house painters. 1216 7

It is well documented that a dietary deficiency in magnesium can induce oxidative stress and an inflammatory response in animal models. In our study, we have investigated these responses in the mouse epididymis after mice had been fed a magnesium-deficient diet for a 2-week duration. The extracellular and intracellular concentrations of magnesium where shown to be depleted on this diet. This was followed, however, only in the liver of the Mg-deficient animals, by an increase in both alpha 2-macroglobulin (alpha-2m), an acute phase marker, and interleukin-6 transcripts suggesting that an inflammatory response had been initiated. These changes were correlated with a decrease in circulating neutrophils. To address the question of whether or not peroxidation was induced in mouse epididymis following hypomagnesia, we have monitored the level of endogenous peroxidation, their ability to respond to induced peroxidation as well as the expression and activity of the enzymatic glutathione peroxidase (GPX) antioxidant family. To evaluate if the epididymis had evolved specific protections against peroxidation, other organs such as the liver and the kidney were monitored in parallel. We detected no evidence for increased peroxidation in any of the mouse organs tested. However, GPX activity was found to be significantly lower in the liver and the kidney of Mg-deficient animals while it was unchanged in the epididymides of the same animals during the deficiency. Histological analysis of the epididymis showed no major difference in the overall cytological aspect of the organ. Segment 2 of the caput, however presented a significant increase in the number of apically located cells or blebbing cells. Immunohistochemical analysis proved that these cells were epididymal apical cells and not infiltrated leukocytes. These observations suggested that the mouse caput epididymidis segment 2 specifically responded to Mg deficiency via the apical cells. Finally, a comparative analysis of stress response genes was conducted in control and magnesium-deficient caput epididymidis samples. It brought forward some genes that might be involved in the peculiar response of the caput epithelium following hypomagnesia.
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PMID:Dietary magnesium depletion does not promote oxidative stress but targets apical cells within the mouse caput epididymidis. 1553 65

The effects of n-acetyl cysteine (NAC), s-allyl cysteine (SAC), s-ethyl cysteine, s-methyl cysteine and s-propyl cysteine (SPC) activity on Balb/cA mice against diabetic complications were examined. These complications included hyperglycemia, hyperlipidemia, oxidation stress, blood coagulation, and cytokine imbalance. To induce diabetes, mice were treated with streptozotocin i.p. for 5 consecutive days. Five cysteine-containing compounds at 1 g/L were added to the drinking water. After intake of the 5 cysteine-containing agents for 4 wk, body weight loss, plasma concentrations of glucose and insulin, and fibronectin levels were improved (P < 0.05) in diabetic mice. The administration of these agents restored the glutathione level (P < 0.05), reduced the loss of catalase and glutathione peroxidase activities in kidney and liver (P < 0.05), and decreased glucose-induced lipid oxidation, as assessed by malondialdehyde formation (P < 0.05). In all diabetic mice, the intake of these agents reduced triglyceride levels in plasma and liver (P < 0.05); however, only NAC, SAC and SPC treatments reduced cholesterol level in liver (P < 0.05). These cysteine-containing agents elevated the activity of 2 fibrinolytic factors, protein C and antithrombin III (P < 0.05). The overexpression of interleukin-6 and tumor necrosis factor-alpha in diabetic mice was suppressed by the intake of the 5 cysteine-containing agents (P < 0.05). Via their antioxidant activities, the 5 compounds effectively improved glycemic control, delayed oxidation damage, downregulated inflammatory cytokines, and enhanced anticoagulant activity in diabetic mice. These data support the multiple roles of these agents as potential protective agents for delaying diabetic deterioration.
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PMID:Five cysteine-containing compounds delay diabetic deterioration in Balb/cA mice. 1557 20


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