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)

Hemodynamic alterations in Russell's viper envenomation are the result of interactions of various vasoactive mediators and perhaps proinflammatory cytokines. Since vascular endothelium is likely to be exposed to high concentrations of the venom and the endothelial cell itself not only plays an important role in the physiologic control of the circulation, but also play a role in inflammation with the synthesis and secretion of proinflammatory cytokines. It was therefore, the objective of this study to determine the effects of Russell's viper venom (RVV) on proinflammatory cytokine production by cultured human umbilical vein endothelial cells (HUVEC) and the release of endothelium-derived substances. Endothelial cells were isolated from freshly obtained human umbilical cord vein and grown in tissue culture to confluence as a homogeneous population. Cells were then incubated at 37 degrees C under 5 per cent CO2 with RVV (0.2, 1.0, 5.0, and 25.0 microg/ml) or lipopolysaccharide (LPS, 10 microg/ml) for 3, 6, 12 and 24 hours. After an indicated time, the levels of endothelin-1 (ET-1); 6-keto-PGF1alpha (a stable metabolite of PGI2) tumor necrosis factor-alpha (TNF-alpha); interleukin-1beta (IL-1beta); and interleukin-6 (IL-6) in supernatants were measured by using ELISA or EIA. The effect of RVV or LPS on cell viability was also measured using MIT assay. The results showed copious amounts of ET-1 production irrespectively with the presence of RVV or LPS. Whereas, production of PGI2 (measured as 6-keto-PGF1alpha, a stable metabolite) was increased significantly higher in the RVV- and LPS-treated EC than in the control EC. However, TNF-alpha and IL-6 productions were not different among these groups. The levels of IL-1beta were very low, although IL-1beta was detectable in the group treated with RVV at a concentration of 25.0 microg/ml. In conclusion, RVV upto 25 microg/ml stimulated PGI2 production by cultured HUVEC. This effect was unlikely related to production of proinflammatory cytokines since LPS or RVV is not sufficient per se to elevate a substantial amount of EC-derived cytokines. The higher amount of IL-6 compared to TNF-alpha and IL-1beta may be produced through other pathways apart from production via a cascade of cytokines. This is the first report showing that RVV up to 25 microg/ml has no effect on prominent proinflammatory cytokine production by HUVEC. However, in blood circulation, the major source of cytokines production is monocyte-macrophage lineage cell. Thus, RVV in blood circulation may activate the production of proinflammatory cytokines mainly from those cells and subsequently induce toxicity.
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PMID:Effects of Russell's viper venom on mediator production in cultured human umbilical vein endothelial cells. 1152 35

The inhalation of antigens does not normally lead to allergic inflammation, but airway resident cells and their products may affect the outcome of antigen exposure. It is therefore important to elucidate how potential allergens interact with airway epithelial cells and other cells located within and below the epithelium. Some studies have indicated that certain antigens, particularly the major house dust mite antigen Der p1, penetrate the airway epithelium by intracellular transportation or paracellular passage, depending on their concentrations, time of exposure, and ability of the cells to inactivate them. If an antigen possesses proteolytic activity, such as Der p1, and it reaches high concentrations or the exposure is prolonged, the disruption of the tight junction can also favor the transepithelial passage of other antigens. In this way, the antigens can easily encounter the effector cells located between epithelial cells and below the basement membrane. The magnitude of this phenomenon may be more prominent in the airways of asthmatic patients, as their epithelium is more permeable to Der p1 than the epithelium of nonasthmatic patients and releases cytokines after exposure to very low concentrations of this antigen for brief periods. Epithelial cell activation may facilitate the development of allergic mucosal sensitization to Der p1 and contribute to the antigen-induced inflammatory response by affecting the migration and function of dendritic cells, mast cells, and eosinophils. Also, there might be a secondary release of interleukin-6 and endothelin-1, which can have a detrimental effect on the cardiovascular function.
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PMID:Allergen-induced generation of mediators in the mucosa. 1154 62

The present study examined the role of calcineurin in insulin-like growth factor (IGF)-1-induced hypertrophy in primary cultures of adult rat ventricular myocytes (ARVM), prepared from the ventricles of 14-16-week-old male Sprague-Dawley rats. The effects of several humoral factors, including phenylephrine, angiotensin II, endothelin-1, IGF-1 and interleukin-6, on the morphology of ARVM were studied. Myocyte surface area was significantly increased by IGF-1 (2,268 +/- 571 to 3,018 +/- 836 microm2, p < 0.01), but not by other humoral factors. This hypertrophic effect of IGF-1 was blocked by genistein (tyrosine kinase inhibitor), PD98059 (MEK inhibitor). These findings suggest that IGF-1 produces ARVM hypertrophy by a tyrosine kinase-MEK mediated pathway as has been reported in neonatal cardiomyocytes. IGF-1-mediated ARVM hypertrophy was also attenuated by cyclosporine A (calcineurin inhibitor), and staurosporine and chelerythrine (protein kinase C inhibitors). IGF-1 markedly increased calcineurin activity (8.7 +/- 1.2 to 98.0 +/- 54.3 pmol x h(-1) mg(-1), p < 0.01), and this activation was completely blocked by pre-treatment with cyclosporine A (8.5 +/- 11.4pmol x h(-1) x mg(-1), p < 0.01) and chelerythrine (2.3 +/- 2.7 pmol x h(-1) mg(-1), p < 0.01). It appears that IGF-1 activates calcineurin by a protein kinase C-dependent pathway. Increased mRNA expression of atrial natriuretic factor by IGF-1 was inhibited by cyclosporine A (p < 0.01). The findings indicate that IGF-1 induces ARVM hypertrophy by protein kinase C and calcineurin-related mechanisms. The fact that elevated calcineurin activity and induced atrial natriuretic factor mRNA expression by IGF-1 were blocked by cyclosporine A further supports the hypothesis that calcineurin is critically involved in IGF-1-induced ARVM hypertrophy.
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PMID:Role of calcineurin in insulin-like growth factor-1-induced hypertrophy of cultured adult rat ventricular myocytes. 1154 82

The aim of this study was to determine the response of inflammatory and vasoactive mediators to 3 consecutive days of exercise in African-American women with and without sickle cell anemia (SCA). Circulating inflammatory mediators [C-reactive protein (CRP), interleukin-6 (IL-6), tumor necrosis factor alpha (TNFalpha)] were measured before, and vasoactive mediators [endothelin-1 (ET-1), nitric oxide metabolites (NOx)] before and after each exercise bout in ten subjects with SCA and ten controls. Exercise did not affect ET-1, IL-6 or CRP concentrations (p >.05). TNFalpha was higher in SCA than controls (p < or = .0005) at all times; however, the response pattern was similar for the groups: no change from day 1 to day 2, but a decrease from day 2 to day 3 (p < or = .05). NOx increased significantly after exercise (p < or = .0001) but returned to baseline by 24 h afterward. On the 3rd day, NOx increased after exercise in SCA but not in the controls (p < or = .05). In conclusion, exercise did not cause a harmful inflammatory response in these individuals with SCA. However, NOx increased after exercise on all 3 days in SCA but appeared attenuated after 2 days in controls.
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PMID:Exercise in sickle cell anemia: effect on inflammatory and vasoactive mediators. 1157 76

The transcription factors nuclear factor interleukin-6 (NF-IL6), early growth response-1 (EGR-1) and hypoxia-inducible factor-1 (HIF-1) have important roles in the molecular pathophysiology of hypoxia-associated pulmonary disease. NF-IL6 controls the production of interleukin (IL)-6 in vascular endothelial cells, which may have anti-inflammatory activity by counteracting effects of IL-1 and IL-8. EGR-1 controls the production of tissue factor by macrophages, which triggers fibrin deposition in the pulmonary vasculature. HIF-1 activates the expression of the vasoconstrictor endothelin-1 in vascular endothelial cells. Angiotensin II induces HIF-1 expression and hypertrophy of pulmonary arterial smooth muscle cells. HIF-1 might therefore have multiple roles in the pathogenesis of pulmonary vascular remodeling.
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PMID:Oxygen-regulated transcription factors and their role in pulmonary disease. 1166 80

Cardiotrophin-1 (CT-1), a member of the interleukin-6 superfamily, and endothelin-1 (ET-1) are potent hypertrophic factors in cardiomyocytes. Although CT-1 and ET-1 gene expression in the heart is upregulated in experimental heart failure, their role in the activation of the cardiac fibroblast is unknown. This study was designed to identify the presence and action of CT-1 and its receptor complex, glycoprotein130 (gp130) and leukemia inhibitory factor (LIF) receptor, on cardiac fibroblast growth in cultured adult canine cardiac fibroblasts. In addition, we investigated the interaction between CT-1/gp130/LIF receptor and ET-1/endothelin type A (ET(A)) receptor axis. Immunohistochemistry was performed using the indirect immunoperoxidase method, while we assessed the cell cycle of cardiac fibroblasts by flow cytometry, DNA synthesis by [(3)H]thymidine incorporation, and collagen synthesis by [(3)H]proline incorporation, respectively. CT-1 and gp130/LIF receptor were widely present in the cytoplasm of the cardiac fibroblasts. Exogenous CT-1 markedly stimulated [(3)H]thymidine and [(3)H]proline incorporations (P<0.01), with accumulation of cells in the S phase. Blockade of gp130 or LIF receptor inhibited basal growth as well as CT-1- or ET-1-stimulated cardiac fibroblast growth. The specific ET(A) receptor antagonist, BQ123, significantly inhibited CT-1-stimulated DNA synthesis. This study demonstrates that CT-1 and its receptors are present in cardiac fibroblasts. In addition, growth of these cells stimulated by endogenous and exogenous CT-1 requires gp130/LIF receptor as well as ET(A) receptor activation. We conclude that gp130/LIF receptor and ET(A) receptor activation are essential for cardiac fibroblast growth by CT-1 and that there is synergism with ET-1/ET(A) receptor axis.
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PMID:Cardiotrophin-1 stimulation of cardiac fibroblast growth: roles for glycoprotein 130/leukemia inhibitory factor receptor and the endothelin type A receptor. 1183 4

Angiotensin-converting enzyme (ACE) inhibitors exert their effects by modulating the neurohumoral milieu. Vasopeptidase inhibitors (VPI) are ACE and neutral endopeptidase inhibitors and may increase natriuretic peptides, bradykinin, and perhaps endothelin-1 in patients with congestive heart failure. Patients (n = 107) with ischemic or dilated cardiomyopathy, New York Heart Association functional class II to III, with left ventricular ejection fraction <40%, and on ACE inhibitor therapy were randomized to either the VPI omapatrilat 40 mg/day or the ACE inhibitor lisinopril 20 mg/day. Trough levels of neurohormones (24 hours after dosing) were assessed at baseline, and at 12 and 24 weeks of follow-up. C-terminal atrial natriuretic peptide (C-ANP) levels decreased with lisinopril (p = 0.035), but not with omapatrilat. In contrast, N-terminal ANP levels did not change, and brain natriuretic peptide (BNP) levels tended to decrease similarly in both groups. Endothelin-1 levels increased in both groups, the increase reaching statistical significance with omapatrilat (p = 0.008). Levels of the proinflammatory cytokine interleukin-6 tended to decrease, and the anti-inflammatory cytokine interleukin-10 increased in both groups, with statistical significance only for interleukin-10 with omapatrilat therapy. Neither agent changed catecholamines or angiotensin II. Thus, even at trough levels, omapatrilat potentiates C-ANP more than lisinopril. Potentially important effects of omapatrilat on endothelin-1 and anti-inflammatory cytokines were identified, providing potential explanations for differences in clinical outcome.
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PMID:Comparison of the effects of omapatrilat and lisinopril on circulating neurohormones and cytokines in patients with chronic heart failure. 1220 9

Patients with congestive heart failure (CHF) have a high incidence of ventricular arrhythmias and sudden arrhythmic death. CHF entails profound and complex abnormalities in humoral responses that are thought to promote arrhythmic events. However, it is unknown which of the many endogenous mediators that accumulate as part of neurohormonal activation is important in arrhythmogenesis in the setting of CHF. The study included 83 patients admitted to the hospital for treatment of decompensated CHF. Neurohormonal and cytokine activation was assessed by measuring plasma renin activity, aldosterone, norepinephrine, endothelin-1, tumor necrosis factor-alpha, and interleukin-6 levels. Atrial and ventricular arrhythmic events were assessed by 24-hour Holter monitoring. In a univariate analysis, a highly significant, positive relationship was found between plasma endothelin-1 levels and the average hourly total premature ventricular beats (P = 0.003), the frequency of ventricular pairs (P = 0.0003), and the frequency of ventricular tachycardia episodes (P = 0.001). After inclusion of clinical variables, drug therapies, neurohormones, and cytokine levels in a multivariate analysis, the positive relationship between plasma endothelin-1 level and the average hourly total premature ventricular beats (P = 0.008), the frequency of ventricular pairs (P = 0.007), and ventricular tachycardia episodes (P = 0.009) remained independent. No association between other neurohormones or cytokines and arrhythmic events was demonstrated. The results of the present study suggest that increased endothelin-1 concentrations may be involved in promoting the occurrence of ventricular ectopy in patients with decompensated CHF. Proarrhythmic effects may account, in part, for the poor outcome associated with increased endothelin-1 levels in patients with decompensated CHF.
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PMID:Neurohumoral activation and ventricular arrhythmias in patients with decompensated congestive heart failure: role of endothelin. 1269 70

We examined the effects of recombinant human C-reactive protein (rhCRP) on atherosclerosis-related factors in cultured human coronary artery endothelial and smooth muscle cells (HCAECs and HCASMCs). After removing endotoxin from commercial rhCRP preparations using the appropriate column, the purified (P)-rhCRP retained the ability to Ca(2+)-dependently bind to phosphorylcholine, but did not augment the secretion of interleukin-6 and MCP-1 from HCAECs, as non-purified (NP)-rhCRP did. By contrast, P-rhCRP elicited 2- to 3-fold increases in the secretion of both hormones from HCASMCs, though the effect was smaller than that obtained with NP-rhCRP. Production of PAI-1 and endothelin-1 was little affected by either rhCRP preparation in either cell type. In addition, P-rhCRP dose-dependently diminished adrenomedullin release from both cell types, but did not affect adrenomedullin receptor expression or function. Our findings highlight the importance of removing endotoxin from commercial rCRP preparations and show that hCRP elicits atherogenic responses from HCASMCs, but not HCAECs.
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PMID:Effects of C-reactive protein on atherogenic mediators and adrenomedullin in human coronary artery endothelial and smooth muscle cells. 1475 Dec 40

Smoking is one of the most important risk factors of atherosclerosis and ischaemic heart disease. Endothelial dysfunction is a pathological result of smoking. The aim of the study was to examine the influence of cigarette smoking on biochemical parameters of endothelial function in persons with angiographically confirmed coronary arteries atherosclerosis. The study group included 117 men: 55 patients (mean age 58.8 +/- 10.4) with ischaemic heart disease and 62 healthy subjects (mean age 47.1 +/- 9.3) of control group. In all patients blood lipid concentrations, biochemical parameters of endothelial function (nitric oxide, endothelin-1, sICAM, selectin-E), and inflammation parameters (interleukin-1 beta, interleukin-6) were measured. In a group of smoking patients both: with atherosclerosis and in control subjects nitric oxide (NO) concentrations in serum were decreased in comparison to nonsmokers. In patients with diagnosed coronary arteries atherosclerosis interleukin-6 and sICAM concentrations were increased in comparison to non-smokers. It is concluded that cigarette smoking activates or maintains inflammatory reaction in vessels with atherosclerotic changes.
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PMID:[Effect of tobacco smoking on endothelial function in patients with coronary arteriosclerosis]. 1508 18


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