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)

Exercise induces increased circulating levels of a number of cytokines. Thus, increased plasma levels of tumour necrosis factor (TNF)-alpha, interleukin (IL-1) beta, IL-1 receptor antagonist (IL-1ra), TNF-receptors (TNF-R), IL-10, IL-8, and macrophage inflammatory protein (MIP)-1 are found after strenuous exercise. The concentration of IL-6 increases up to 100 fold after a marathon race. Recently, it has been demonstrated that IL-6 is produced locally in contracting skeletal muscles and that the net release from the muscle can account for the exercise-induced increase in arterial IL-6 concentration. IL-6 more than any other cytokine is produced in large amounts in response to exercise. It is produced locally in the skeletal muscle in response to exercise, and IL-6 is known to induce hepatic glucose-output and to induce lipolysis. This indicates that IL-6 may represent an important link between contracting skeletal muscles and exercise-related metabolic changes.
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PMID:Exercise and cytokines with particular focus on muscle-derived IL-6. 1157 46

1. 3-Hydroxy-3-methylglutaryl co-enzyme A reductase inhibitors (statins) prevent the progression of atherosclerosis by lowering cholesterol. However, the effect of statins on the synthesis of pro-inflammatory cytokines from endothelial cells has not yet been fully investigated. Here, we examined the effect of pravastatin, one of the statins, on IL-8 synthesis induced by thrombin in human aortic endothelial cells (AoEC) cultured with high glucose concentrations. 2. Pravastatin significantly decreased the IL-8 synthesis induced by thrombin. 3. Pravastatin inhibited the p44/42 MAP kinase activity induced by thrombin, but did not inhibit the p38 MAP kinase activity. 4. Translocation of ras protein from the cytosol to plasma membrane was inhibited by pravastatin. 5. Pravastatin inhibit the activator protein-1 activity, but did not inhibit the activation of IkappaB-alpha. 6. Dominant negative ras inhibited the p44/42 MAP kinase activity induced by PMA. 7. Our results suggest that pravastatin inhibits IL-8 synthesis by blocking the ras-MAP (p44/42) kinase pathway rather than nuclear factor-kappaB. Pravastatin may prevent atherosclerosis not only by lowering cholesterol levels, but also by suppressing IL-8 synthesis in AoEC through the inhibition of p44/42 MAP kinase, and this may be more beneficial in diabetic patients than in non-diabetics.
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PMID:Pravastatin suppresses the interleukin-8 production induced by thrombin in human aortic endothelial cells cultured with high glucose by inhibiting the p44/42 mitogen activated protein kinase. 1160 15

The effects of shear stress on interleukin 8 (IL-8) production by human umbilical vein endothelial cells (HUVEC) were studied by subjecting the HUVEC to a steady flow laminar shear stress of up to 0.7 N/m(2) in a parallel plate flow chamber. Shear stress decreased IL-8 mRNA expression in a dose and time-dependent fashion. High glucose concentrations increased IL-8 mRNA levels in a MAPK-p38-dependent manner, which was suppressed by shear stress. Measurement of IL-8 protein in HUVEC culture media by ELISA demonstrated that IL-8 secretion was also increased by high glucose and suppressed by shear stress. These results suggest that the anti-atherogenic effect of shear stress arises partly from the suppression of the production of IL-8 which has been shown to trigger the adhesion of monocytes to a vascular endothelium and also acts as a mitogen and chemoattractant for vascular smooth muscle cells.
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PMID:Fluid shear stress suppresses interleukin 8 production by vascular endothelial cells. 1167 49

Hyperglycaemia, in insulin-dependent or independent diabetes mellitus, promotes endothelial cell (EC) dysfunction and is a major factor in the development of macro- or microvascular diseases. The mechanisms and the disease-related genes in vascular diseases resulting from hyperglycaemia are poorly understood. Macroarrays. bearing a total of 588 cDNA known genes, were used to analyze HUVEC gene transcription subjected to 25 or 5-mM glucose for 24 h. Isolated mRNA derived from treated first passage HUVEC were reverse transcribed, 32P labeled, and hybridized to the cDNA macroarrays. Results show that acute hyperglycaemia induces an up-regulation of seven major genes, four of which were not previously reported in the literature. Northern blot analyses, performed on these 4 genes, confirm macroarrays results for alphav, beta4, c-myc, and MUC18. Moreover, time course analysis (0, 2, 4, 8, 2, 16, 24 h) of alphav, beta4 c-myc, and MUC18 mRNA expression, observed by northern blot assays, showed a peak at time points situated between 2 to 8 h. The 3 other genes (ICAM-1, beta1, and IL-8), were shown by others to be significantly upregulated after glucose stimulation. Furthermore, ELISA assays performed on the supernatant of HUVEC culture medium showed a significant increase of IL-8 for cells treated with 25-mM compared to 5-mM glucose. Identified genes, upregulated in endothelial cells as a result of acute hyperglycaemia, may serve as therapeutic or diagnostic targets in vascular lesions present in diabetic patients. These results also demonstrate the use of cDNA macroarrays as an effective approach in identifying genes implicated in a diseased cell.
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PMID:Acute hyperglycaemia induces changes in the transcription levels of 4 major genes in human endothelial cells: macroarrays-based expression analysis. 1184 44

It has been reported that alpha-tocopherol, an antioxidant agent, may play a role in preventing diabetic angiopathy. However, there is little evidence to show the effect of alpha-tocopherol on the production of pro-inflammatory cytokines in endothelial cells. Therefore, we examined the effect of alpha-tocopherol on the regulation of IL-8 synthesis induced by high glucose and/or thrombin in endothelial cells. Thrombin alone markedly increased the IL-8 release. Furthermore, high glucose levels and thrombin combined had additive effects on IL-8 synthesis, and alpha-tocopherol diminished their effect; alpha-tocopherol also inhibited the phosphorylation of IkappaB-alpha induced by high glucose levels and/or thrombin. Our results suggest that the administration of alpha-tocopherol to diabetic patients may have a beneficial effect for the prevention of diabetic vascular complications by the inhibition of IL-8 synthesis from endothelial cells.
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PMID:alpha-Tocopherol Inhibits IL-8 synthesis induced by thrombin and high glucose in endothelial cells. 1197 86

Obesity is associated with the increased risk of cardiovascular disease; however, mechanisms responsible for such an increase are not fully understood. IL-8 is a cytokine that might have atherogenic properties. Recent in vitro studies revealed that IL-8 is produced and secreted by human adipocytes. The aim of the present study was to evaluate plasma IL-8 concentrations in obese subjects and the relationships between circulating IL-8 and anthropometric and biochemical parameters and TNF-alpha system. A total of 75 subjects with normal glucose tolerance, 35 lean and 40 obese, were recruited for this study. Plasma IL-8 levels were measured in fasting state, after an oral glucose tolerance test and after the euglycemic hyperinsulinemic clamp. A significant increase in plasma IL-8 was observed in the obese group. In simple regression analysis, performed for the initial evaluation of relationships, plasma IL-8 was related to body mass index, percentage of body fat, fat mass (FM), and soluble TNF-alpha receptor 2 (sTNFR2) in both groups and with waist-to-hip ratio and sTNFR1 in the obese. In multiple regression analysis, FM, waist-to-hip ratio, gender, sTNFR2, and low density lipoprotein cholesterol were responsible for 44% of IL-8 variability. During oral glucose tolerance testing, mean plasma IL-8 concentrations increased in both groups, whereas clamp resulted in a significant increase in plasma IL-8 only in the obese. We conclude that plasma IL-8 levels are increased in obese subjects, and are related to FM and TNF-alpha system. Increase in circulating IL-8 might be one of the factors linking obesity with greater cardiovascular risk.
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PMID:Plasma interleukin-8 concentrations are increased in obese subjects and related to fat mass and tumor necrosis factor-alpha system. 1236 41

Resistin, also known as Fizz3 or ADSF, is a protein found in murine adipose tissue and inflammatory lung exudates. The present studies found that resistin was released by explants of human adipose tissue but the release was quite variable ranging from 3 to 158 ng/g over 48 h. The release of resistin was 250% greater by explants of omental than by explants of human subcutaneous abdominal adipose tissue. Resistin release by adipocytes was negligible as compared to that by the non-fat cells of adipose tissue. Leptin formation by adipocytes was 8-fold greater than its formation by the non-fat cells, while the formation of PAI-1 by adipocytes was 38% of that by the non-fat cells. The conversion of glucose to lactate as well as the formation of PGE(2) and IL-8 was approximately 15% of that by the non-fat cells. In contrast the release of IL-6 and IL-1beta by adipocytes was 4-7% of that by the non-fat cells while the formation of resistin and IL-10 by adipocytes was 2% of that by non-fat cells. The release of adiponectin by explants ranged from 1000 to 5000 ng/g over 48 h but did not correlate with that of resistin. The present data suggest that resistin release by explants of human adipose tissue in primary culture is largely derived from the non-fat cells present in the explants.
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PMID:Resistin release by human adipose tissue explants in primary culture. 1250 2

Sixteen experienced marathoners ran on treadmills for 3 h at approximately 70% maximal oxygen consumption (Vo(2 max)) on two occasions while receiving 1 l/h carbohydrate (CHO) or placebo (Pla) beverages. Blood and vastus lateralis muscle biopsy samples were collected before and after exercise. Plasma was analyzed for IL-6, IL-10, IL-1 receptor agonist (IL-1ra), IL-8, cortisol, glucose, and insulin. Muscle was analyzed for glycogen content and relative gene expression of 13 cytokines by using real-time quantitative RT-PCR. Plasma glucose and insulin were higher, and cortisol, IL-6, IL-10, and IL-1ra, but not IL-8, were significantly lower postexercise in CHO vs. Pla. Change in muscle glycogen content did not differ between CHO and Pla (P = 0.246). Muscle cytokine mRNA content was detected preexercise for seven cytokines in this order (highest to lowest): IL-15, TNF-alpha, IL-8, IL-1beta, IL-12p35, IL-6, and IFN-gamma. After subjects ran for 3 h, gene expression above prerun levels was measured for five of these cytokines: IL-1beta, IL-6, and IL-8 (large increases), and IL-10 and TNF-alpha (small increases). The increase in mRNA (fold difference from preexercise) was attenuated in CHO (15.9-fold) compared with Pla (35.2-fold) for IL-6 (P = 0.071) and IL-8 (CHO, 7.8-fold; Pla, 23.3-fold; P = 0.063). CHO compared with Pla beverage ingestion attenuates the increase in plasma IL-6, IL-10, and IL-1ra and gene expression for IL-6 and IL-8 in athletes running 3 h at 70% Vo(2 max) despite no differences in muscle glycogen content.
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PMID:Carbohydrate ingestion influences skeletal muscle cytokine mRNA and plasma cytokine levels after a 3-h run. 1253 3

Perfluorocarbonic blood substitute Perftoran (PF) was used in combined intensive therapy of 79 patients with severe viral hepatitis B as a polyfunctional pathogenetic drug according to the following scheme: intravenously 400 ml 1-2 times a day for 2-6 days (800-2400 ml per course). PF exhibited immunomodulating, antioxidant, membrane-stabilizing and disintoxicating properties. The immunomodulating effect of the drug manifested itself in its influence on functional activity of macrophages, reduction of their oversection of proinflammatory cytokines: IL-1 beta, IL-6, IL-8, TNF-alpha. Antioxidant properties were established on the basis of the ability of PF to lower activity of prooxidant factors (myeloperoxidase of neutrophilic granulocytes) and to stimulate antioxidant factors (catalase, glucose-6-phosphatedehydrogenase), reduced glutathione in erythrocytes). As a membranostabilizer, PF increased resistance of erythrocyte membranes to peroxide hemolysis and improved their rheological indices (deformability and viscosity). A disintoxication effect of PF led to reduction of middle-molecular peptides content in plasma. PF had a noticeable effect on basic clinicobiochemical indices in patients with a severe course of viral hepatitis B as well as the disease course and outcomes. Finally, PF reduced the duration of treatment of patients with severe viral hepatitis B in hospital and intensive care units. It is inferred that administration of infusion drugs on the basis of perfluorocarbonic compounds holds promise in pathogenetic therapy of viral hepatitides.
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PMID:[Perfluorocarbonic compounds application as a new approach in pathogenic treatment of severe forms of viral hepatitis]. 1285 70

Several studies have shown a relationship between interleukin (IL) 6 levels and insulin resistance. We here show that human subcutaneous adipose cells, like 3T3-L1 cells, are target cells for IL-6. To examine putative mechanisms and cross-talk with insulin, 3T3-L1 adipocytes were cultured for different times with IL-6 and tumor necrosis factor alpha (TNF-alpha). IL-6, in contrast to TNF-alpha, did not increase pS-307 of insulin-receptor substrate (IRS)-1 or JNK activation. However, IL-6, like TNF-alpha exerted long term inhibitory effects on the gene transcription of IRS-1, GLUT-4, and peroxisome proliferator-activated receptor gamma. This effect of IL-6 was accompanied by a marked reduction in IRS-1, but not IRS-2, protein expression, and insulin-stimulated tyrosine phosphorylation, whereas no inhibitory effect was seen on the insulin receptor tyrosine phosphorylation. Consistent with the reduced GLUT-4 mRNA, insulin-stimulated glucose transport was also significantly reduced by IL-6. An important interaction with TNF-alpha was found because TNF-alpha markedly increased IL-6 mRNA and protein secretion. These results show that IL-6, through effects on gene transcription, is capable of impairing insulin signaling and action but, in contrast to TNF-alpha, IL-6 does not increase pS-307 (or pS-612) of IRS-1. The link between IL-6 and insulin resistance in man was further corroborated by the finding that the expression of IL-6, like that of TNF-alpha and IL-8, was markedly increased ( approximately 15-fold) in human fat cells from insulin-resistant individuals. We conclude that IL-6 can play an important role in insulin resistance in man and, furthermore, that it may act in concert with other cytokines that also are up-regulated in adipose cells in insulin resistance.
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PMID:Interleukin-6 (IL-6) induces insulin resistance in 3T3-L1 adipocytes and is, like IL-8 and tumor necrosis factor-alpha, overexpressed in human fat cells from insulin-resistant subjects. 1295 69


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