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)

Human adipose tissue has an important protein secretory function. Cytokines, hormones, prohormones and enzymes are secreted from fat cells and act in an endocrine or paracrine fashion. The production of several of these proteins is affected by obesity; normally there is an increase in the obese state. Protein production is, as a metabolic activity, subject to regional variations. In particular, the production of leptin, angiotensinogen, interleukin-6 and plasmin activator inhibitor-1 differs between subcutaneous and visceral adipose tissue sites, but no regional differences have been reported in the production of tumour necrosis factor alpha. It is possible that regional variations in protein production by adipose tissue are of importance in some of the endocrine and metabolic disturbances seen in various forms of obesity, such as visceral and upper-body obesity.
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PMID:Regional differences in protein production by human adipose tissue. 1135 30

Despite extensive research, the exact mechanisms of cyclosporine A (CsA)-induced hypertension and nephrotoxicity remain obscure. Several lines of evidence suggest an involvement of the renin-angiotensin system (RAS) in CsA toxicity, but the issue is still controversial in more ways than one. Some interesting data of the interaction of CsA and RAS have been presented by us and others during the last years. In rats, activation of RAS by CsA is a consistent finding while the results from clinical studies show controversial results. The mechanisms of activation of RAS may be multifactorial. CsA increases renin release directly from juxtaglomerular cells. However, RAS activation may at least partly account for glomerular ischemia by vasoconstriction. A totally different view about the interaction of CsA and RAS has recently been presented. CsA antagonised the harmful effects of RAS over-expression on renal damage in double transgenic rats harbouring human renin and angiotensinogen genes. The protection was due to anti-inflammatory properties of CsA by inhibition of interleukin-6 and inducible nitric oxide synthase (iNOS) expression. Other studies have confirmed the inhibitory effect of CsA on iNOS. Calcium antagonists have been proposed to be the antihypertensive drugs of choice in treatment of CsA-induced hypertension because of their favourable haemodynamic effects on the kidneys. However, because angiotensin II plays a major role in the development of CsA-induced structural renal damage, pharmacological inhibition of RAS in CsA-treatment may have some beneficial effects beyond blood pressure control.
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PMID:Interaction of cyclosporine A and the renin-angiotensin system; new perspectives. 1187 76

The present study was designed to clarify the role of angiotensin II (Ang II) in modulating renal tumor necrosis factor (TNF)-alpha and interleukin-6 (IL-6) production and to investigate the effect of one dose of Ang II inhibitor on cytokines production following lipopolysaccharide (LPS) to cause endotoxemia. Two studies were performed: 1) Ang II was infused intravenously at a rate of 0.2 microg/kg per minute for 4 h in rats and then kidneys were collected to assay TNF-alpha and IL-6 mRNA levels; 2) Four-week-old Wistar rats pre-treated with angiotensin-converting enzyme inhibitor, enalapril, or type I Ang II-receptor antagonist, TCV-116, were injected with LPS (0.1, 0.5, 1.0 mg, i.p.), and then 2 or 4 h later, kidneys were collected to assay TNF-alpha, IL-6, renin and angiotensinogen mRNA levels. After a 4-h intravenous infusion of Ang II, renal TNF-alpha or IL-6 mRNA level significantly increased 1.9-fold or 2.1-fold (each P<0.05) to the control level, respectively. LPS stimulated TNF-alpha, IL-6 and angiotensinogen mRNA levels in the kidney but in rats given enalapril or TCV-116, LPS-induced IL-6 and TNF-alpha mRNA levels were completely suppressed (each P<0.05). This suggests that a single dose of renin-angiotensin system inhibitor suppressed renal IL-6 and TNF-alpha production and may prevent cytokine-induced renal damage during endotoxemia.
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PMID:Suppression of endotoxin-induced renal tumor necrosis factor-alpha and interleukin-6 mRNA by renin-angiotensin system inhibitors. 1192 13

Hypertension is a serious health problem in Western society, in particular for the African-American population. Although previous studies have suggested that the angiotensinogen (AGT) gene locus is involved in human essential hypertension, the molecular mechanisms involved in hypertension in African-Americans remain unknown. We show that an A/G polymorphism at -217 in the promoter of the AGT gene plays a significant role in hypertension in African-Americans. The frequency of the -217A allele was increased significantly in African-American hypertensive subjects compared with normotensive controls. We also show that the nucleotide sequence of this region of the AGT gene promoter bound strongly to CAAT/enhancer-binding protein (C/EBP) family transcription factors when nucleoside A was present at -217. In addition, we show that reporter constructs containing the human AGT gene promoter with nucleoside A at -217 had increased basal transcriptional activity upon transient transfection in HepG2 cells compared with reporter constructs with nucleoside G at -217. Finally, we show that interleukin-6 treatment in the presence or absence of overexpressed C/EBPbeta increased the promoter activities of reporter constructs containing nucleoside A at -217 compared with reporter constructs containing nucleoside G at -217. Because the AGT gene is expressed primarily in liver and adipose tissue, and C/EBP family transcription factors play an important role in gene expression in these tissues, we propose that increased transcriptional activity of the -217A allele of the human AGT gene is associated with hypertension in African-Americans.
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PMID:Angiotensinogen gene polymorphism at -217 affects basal promoter activity and is associated with hypertension in African-Americans. 1214 90

It is now well established that vascular inflammation is an independent risk factor for the development of atherosclerosis. In otherwise healthy patients, chronic elevations of circulating interleukin-6 or its biomarkers are predictors for increased risk in the development and progression of ischemic heart disease. Although multifactorial in etiology, vascular inflammation produces atherosclerosis by the continuous recruitment of circulating monocytes into the vessel wall and by contributing to an oxidant-rich inflammatory milieu that induces phenotypic changes in resident (noninflammatory) cells. In addition, the renin-angiotensin system (RAS) has important modulatory activities in the atherogenic process. Recent work has shown that angiotensin II (Ang II) has significant proinflammatory actions in the vascular wall, inducing the production of reactive oxygen species, inflammatory cytokines, and adhesion molecules. These latter effects on gene expression are mediated, at least in part, through the cytoplasmic nuclear factor-kappaB transcription factor. Through these actions, Ang II augments vascular inflammation, induces endothelial dysfunction, and, in so doing, enhances the atherogenic process. Our recent studies have defined a molecular mechanism for a biological positive-feedback loop that explains how vascular inflammation can be self-sustaining through upregulation of the vessel wall Ang II tone. Ang II produced locally by the inflamed vessel induces the synthesis and secretion of interleukin-6, a cytokine that induces synthesis of angiotensinogen in the liver through a janus kinase (JAK)/signal transducer and activator of transcription (STAT)-3 pathway. Enhanced angiotensinogen production, in turn, supplies more substrate to the activated vascular RAS, where locally produced Ang II synergizes with oxidized lipid to perpetuate atherosclerotic vascular inflammation. These observations suggest that one mechanism by which RAS antagonists prevent atherosclerosis is by reducing vascular inflammation. Moreover, antagonizing the vascular nuclear factor-kappaB and/or hepatic JAK/STAT pathways may modulate the atherosclerotic process.
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PMID:Vascular inflammation and the renin-angiotensin system. 1217 84

Visceral adipose tissue (VAT) imaged by computed tomography (CT) or magnetic resonance imaging (MRI) is associated with the metabolic syndrome features, being morphologically and functionally different from subcutaneous adipose tissue (SAT). Insulin effect is lower and catecholamine effect higher in visceral adipose tissue, with its metabolites and its secretions draining through portal system, partially at least, to the liver. Thus, visceral cells transfer and release fatty acids more extensively, have increased glucocorticoid and reduced thiazolidinedione responses, produce more angiotensinogen, interleukin-6 and plasminogen activator inhibitor-1, and secrete less leptin and adiponectin than SAT. Furthermore, there are regional differences in the intrinsic characteristics of the preadipocytes, with those of SAT presenting greater differentiation and fat cell gene expression but less apoptosis than that of VAT. All features contribute to the morbidity associated with increased VAT. To evaluate the relationship between VAT and components of the metabolic syndrome, 55 non-diabetic women, 11 lean (VAT < 68 cm 2) and 44 obese were studied. The obese with VAT within the normal range (VAT < or = 68 cm 2) had higher BMI, WHR, BP and resistance to FFA suppression during oGTT in comparison to the lean controls. The obese with VAT > 68 cm 2 compared to those with VAT < or = 68 cm 2 had similar body mass index (BMI) but significantly higher in vivo homeostasis model assessment for insulin resistance (HOMA IR ) results and triglycerides. By pooling all data, correlation analysis indicated that VAT contributes more to insulin resistance (HOMA IR ) than SAT does, but not when insulin-suppressed plasma free fatty acids during oral glucose tolerance test as an index of insulin resistance are taken into consideration.
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PMID:Depot-specific hormonal characteristics of subcutaneous and visceral adipose tissue and their relation to the metabolic syndrome. 1266 Aug 70

Obesity is associated with increased incidence of cardiovascular mortality. However, the mechanisms that link increased fat mass with hypercholesterolemia, hypertension, endothelial dysfunction and coronary heart disease have not been fully elucidated. Unravelling the diverse neuroendocrine systems, which regulate energy balance and body fat has been a long-standing challenge in biology, with obesity as an increasingly important public health focus. Until recently, the adipocyte has been considered only a passive tissue for the storage of excess energy in the form of fat. However, there is now compelling evidence that adipocytes act as endocrine, secretory cells. It has been shown that several hormones, growth factors and cytokines are actually expressed in white adipose tissue. In a dynamic view of the adipocyte a wide range of signals emanates from white adipose tissue such as tumour necrosis factor-alpha (TNF-alpha), interleukin-6 (IL-6), and their respective soluble receptors. White adipose tissue also secretes important regulators of lipoprotein metabolism like lipoprotein lipase (LPL), apolipoprotein E (apoE) and cholesteryl ester transfer protein (CETP). The increasing number of products secreted by adipocytes also includes leptin, estrogen, angiotensinogen, plasminogen activator inhibitor-1 (PAI-1), tissue factor and transforming growth factor-beta (TGF-beta). Nitric oxide synthase (NOS) has been also reported to be expressed in white adipose tissue. Acylation stimulating protein (ASP), adipophilin, adipoQ, adipsin, monobutyrin, agouti protein and factors related to pro-inflammatory and immune processes have also been shown to be released by white adipocytes. Since blood vessels express receptors for most of the adipocyte-derived factors, adipose tissue seems to play a key role in cardiovascular physiology through the existence of a network of local and systemic signals. The current knowledge in this field will be reviewed in the broader perspective of cardiovascular physiology and pathophysiology.
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PMID:The adipose tissue as a source of vasoactive factors. 1532 Jul 86

The traditional function attributed to white adipose tissue of energy storage in the form of triglycerides has been challenged by results from recent studies, showing that adipose tissue is, in fact, a highly active metabolic and endocrine organ. A radical change in perspective followed the discovery of a large number of proteins secreted from white adipocytes, such as leptin, resistin, adiponectin, adipsin, acylation-stimulating protein, angiotensinogen, tumour necrosis factor a, interleukin-6, retinol-binding protein, plasminogen activator inhibitor-1, tissue factor, fasting-induced adipose factor, fibrinogen/angiopoetin-related protein, and metallothionein. The effects of specific proteins may be either autocrine or paracrine, meaning that they might act in adipose tissue itself or in more distant target tissues. Some of these proteins induce insulin resistance, some play a role in glucose and lipid metabolism, some are inflammatory cytokines, while others are involved in vascular haemostasis. The key challenges for future investigations of adipose tissue's secretory functions will be to identify all of its secreted proteins, to establish the function of each secreted protein, and to assess the pathophysiological consequences of changes in adipocyte protein production due to problems, such as obesity, fasting, or diabetes mellitus type 2.
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PMID:[Adipose tissue as an endocrine organ]. 1664 Jan 91

Cytokines are emerging as important in developmental processes. They may induce alterations in normal gene expression patterns, activate angiotensinogen transcription, or alter expression of the renin-angiotensin system (RAS). To determine whether prenatal exposure to interleukin-6 (IL-6) influences gene expression of the intrarenal RAS and contributes to renal dysfunction and hypertension in adulthood, we exposed female rats to IL-6 early (EIL-6 females) and late (LIL-6 females) in pregnancy and analysed blood pressure in the offspring at 5-20 weeks of age. Renal fluid and electrolyte excretion was assessed in clearance experiments, mRNA expression by real-time PCR, and protein levels by Western blot. Systolic pressure was increased at 5 weeks in IL-6 females and at 11 weeks in males. Circulatory RAS levels were increased in all IL-6 females, but angiotensin-1-converting enzyme (ACE) activity was increased only in LIL-6 females. LIL-6 males and IL-6 females showed decreased urinary flow rate and urinary sodium and potassium excretion. Dopamine excretion was decreased IL-6 females. In adult renal cortex, renin expression was increased in all IL-6 females, but angiotensinogen mRNA was increased only in LIL-6 females; AT(1) receptor (AT(1)-R) mRNA and protein levels were increased in LIL-6 females, whereas AT(2) receptor (AT(2)-R) levels were decreased in LIL-6 females and EIL-6 males. In adult renal medulla, AT(1)-R protein levels were increased in LIL-6 females, and AT(2)-R mRNA and protein levels were decreased in EIL-6 males and LIL-6 females. Prenatal IL-6 exposure may cause hypertension by altering the renal and circulatory RAS and renal fluid and electrolyte excretion, especially in females.
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PMID:Prenatal exposure to interleukin-6 results in hypertension and alterations in the renin-angiotensin system of the rat. 1682 9

The present study aimed to investigate the effects of olmesartan, an antagonist for angiotensin II receptor type 1(AT1), on the activation of extracellular signal-regulated kinases (ERK)1/2, tissue remodeling, and pro-inflammatory signals in the right ventricle and lung of mice during the early phase of hypobaric hypoxia. Phosphorylation of ERK1/2 in both tissue types in response to hypoxia peaked at 1-3 days, and declined rapidly in the right ventricle, whereas in the lung it was sustained for at least 8 days. Upregulation of angiotensinogen mRNA was observed in the hypoxic lung at 4-9 days, but not in the hypoxic right ventricle and pulmonary artery. Olmesartan inhibited the hypoxia-induced phosphorylation of ERK1/2 in the lung, but not in the right ventricle. Neither right ventricular hypertrophy nor the thickening of the intrapulmonary arterial wall was ameliorated by olmesartan. However, this drug inhibited the expression of the mRNA for angiotensinogen and several pro-inflammatory factors, including interleukin-6 and inducible nitric oxide synthase in the hypoxic lung. These results suggest that olmesartan blocks a potential positive feedback loop of the angiotensin II-AT1 receptor system, which may lead to attenuate pro-inflammatory signals in the mouse lung, that are associated with hypoxic pulmonary hypertension, without inducing any appreciable effects on the compensatory cardiopulmonary hypertrophy at an early phase of exposure to a hypobaric hypoxic environment.
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PMID:Effects of olmesartan, an AT1 receptor antagonist, on hypoxia-induced activation of ERK1/2 and pro-inflammatory signals in the mouse lung. 1708 97


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