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)

White adipose tissue is now recognised to be a multifunctional organ; in addition to the central role of lipid storage, it has a major endocrine function secreting several hormones, notably leptin and adiponectin, and a diverse range of other protein factors. These various protein signals have been given the collective name 'adipocytokines' or 'adipokines'. However, since most are neither 'cytokines' nor 'cytokine-like', it is recommended that the term 'adipokine' be universally adopted to describe a protein that is secreted from (and synthesised by) adipocytes. It is suggested that the term is restricted to proteins secreted from adipocytes, excluding signals released only by the other cell types (such as macrophages) in adipose tissue. The adipokinome (which together with lipid moieties released, such as fatty acids and prostaglandins, constitute the secretome of fat cells) includes proteins involved in lipid metabolism, insulin sensitivity, the alternative complement system, vascular haemostasis, blood pressure regulation and angiogenesis, as well as the regulation of energy balance. In addition, there is a growing list of adipokines involved in inflammation (TNFalpha, IL-1beta, IL-6, IL-8, IL-10, transforming growth factor-beta, nerve growth factor) and the acute-phase response (plasminogen activator inhibitor-1, haptoglobin, serum amyloid A). Production of these proteins by adipose tissue is increased in obesity, and raised circulating levels of several acute-phase proteins and inflammatory cytokines has led to the view that the obese are characterised by a state of chronic low-grade inflammation, and that this links causally to insulin resistance and the metabolic syndrome. It is, however, unclear as to the extent to which adipose tissue contributes quantitatively to the elevated circulating levels of these factors in obesity and whether there is a generalised or local state of inflammation. The parsimonious view is that the increased production of inflammatory cytokines and acute-phase proteins by adipose tissue in obesity relates primarily to localised events within the expanding fat depots. It is suggested that these events reflect hypoxia in parts of the growing adipose tissue mass in advance of angiogenesis, and involve the key controller of the cellular response to hypoxia, the transcription factor hypoxia inducible factor-1.
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PMID:Adipokines: inflammation and the pleiotropic role of white adipose tissue. 1546 38

Explants of human adipose tissue from nonobese subjects were cultured for 24 h with or without the presence of 20 ng/ml TNFalpha. Gene expression and/or medium concentrations of interleukin (IL)-1beta, IL-1 receptor antagonist (IL-1 RA), TNFalpha, IL-6, IL-8, resistin, PAI-1 and leptin were analysed. TNFalpha increased the mRNA levels of TNFalpha itself as well as IL-6, IL-8, IL-1beta and PAI-1, but not leptin. The medium concentrations of IL-1 RA, IL-6 and IL-8 were markedly increased by TNFalpha while no measurable release of TNFalpha, resistin or IL-1beta to the medium was found. Thus, human adipose tissue from nonobese individuals releases substantial amounts of IL-6, IL-8 and IL-1 RA and the gene expression of these cytokines, like that of IL-1beta and PAI-1, is regulated by TNFalpha. However, since neither TNFalpha, resistin or IL-1beta was found in the culture medium, such a regulatory effect by TNFalpha on adipose tissue in vivo is likely to be mediated through a paracrine mechanism where invaded inflammatory cells may play a critical role.
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PMID:Cytokine release from adipose tissue of nonobese individuals. 1591 41

Adipose tissue has been recognised as the quantitatively most important energy store of the human body for many years, in addition to its functions as mechanical and thermic insulator. In mammals, the adipose organ is localised in several depots including white as well as brown adipose tissues. The largest depots are found subcutaneously and in the abdominal region. Several secretory proteins are synthesised in adipose tissue including leptin, resistin, adiponectin, tumor necrosis factor (TNFalpha), angiotensinogen, adipsin, acylation-stimulating protein, retinol-binding protein (RBP), interleukin (IL)-1b, IL-6, IL-8, IL-10, plasminogen activator inhibitor-1 (PAI-1), fasting-induced adipose factor, fibrinogen-angiopoietin-related protein, metallothionein, tissue factor (TF), complement C3, fibronectin, haptoglobin, entactin/nidogen, collagen VI alpha 3, pigment epithelium-derived factor (PEDF), hippocampal cholinergic neurostimulating peptide (HCNP), neutrophil gelatinase-associated lipocalin (NGAL) and adiponutrin. Fatty acids may influence the expression of adipokines like leptin, resistin or adiponectin directly by interaction with transcription factors, or indirectly via unknown mechanisms possibly linked to fatty acid oxidation, synthesis or storage. Because fatty acids are the main components of adipose tissue, it is of essential interest to clarify the biological effects of different types of fatty acids on the expression of relevant adipokines.
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PMID:Fatty acids and expression of adipokines. 1594 95

Obesity is characterized by an expanded adipose tissue mass. Recent data suggest that adipose tissue is a multi-functional organ rather than simply a passive storage site for excess energy. It has been clearly demonstrated that human adipose tissue produces a variety of secretory factors that exert multiple effects at both the local and the systemic level. To date, >100 products, covering a broad range of protein families as well as many fatty acids and prostaglandins, have been reported to be secreted by adipose tissue. The source of these secreted factors is not only mature fat cells but also poorly-identified cells present in the stromal-vascular fraction including macrophages. Secreted factors of particular interest include many cytokines or chemokines, such as TNF-alpha, IL-6, IL-8, as well as plasminogen activator inhibitor-1, angiotensin-II, leptin, and adiponectin. In the obese state the expression and secretion of these factors is disturbed. With the exception of adiponectin, most circulating factors are elevated. From this perspective, obesity can be described as a pro-inflammatory condition. In addition, regional differences in adipose expression of many of these factors have been found. There is now growing evidence that many secretory factors play an important role in the pathophysiology of the metabolic and cardiovascular complications of obesity. The question arising from these observations is how the secretory pattern of adipose tissue can be modified by dietary and pharmacological measures to reduce the health risks of obesity.
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PMID:Secretory factors from human adipose tissue and their functional role. 1596 Aug 61

Cardiovascular disease (CVD) is the leading cause of morbidity and mortality in the Western world. Its incidence has also been increasing lately in developing countries. Several lines of evidence support a role for oxidative stress and inflammation in atherogenesis. Oxidation of lipoproteins is a hallmark in atherosclerosis. Oxidized low-density lipoprotein induces inflammation as it induces adhesion and influx of monocytes and influences cytokine release by monocytes. A number of proinflammatory cytokines such as interleukin-1beta (IL-1beta), IL-6, and tumor necrosis factor-alpha (TNF-alpha) modulate monocyte adhesion to endothelium. C-reactive protein (CRP), a prototypic marker of inflammation, is a risk marker for CVD and it could contribute to atherosclerosis. Hence, dietary micronutrients having anti-inflammatory and antioxidant properties may have a potential beneficial effect with regard to cardiovascular disease. Vitamin E is a potent antioxidant with anti-inflammatory properties. Several lines of evidence suggest that among different forms of vitamin E, alpha-tocopherol (AT) has potential beneficial effects with regard to cardiovascular disease. AT supplementation in human subjects and animal models has been shown to decrease lipid peroxidation, superoxide (O2-) production by impairing the assembly of nicotinamide adenine dinucleotide phosphate (reduced form) oxidase as well as by decreasing the expression of scavenger receptors (SR-A and CD36), particularly important in the formation of foam cells. AT therapy, especially at high doses, has been shown to decrease the release of proinflammatory cytokines, the chemokine IL-8 and plasminogen activator inhibitor-1 (PAI-1) levels as well as decrease adhesion of monocytes to endothelium. In addition, AT has been shown to decrease CRP levels, in patients with CVD and in those with risk factors for CVD. The mechanisms that account for nonantioxidant effects of AT include the inhibition of protein kinase C, 5-lipoxygenase, tyrosine-kinase as well as cyclooxygenase-2. Based on its antioxidant and anti-inflammatory activities, AT (at the appropriate dose and form) could have beneficial effects on cardiovascular disease in a high-risk population.
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PMID:Vitamin E, oxidative stress, and inflammation. 1601 63

White adipose tissue (WAT) is now recognized as a major endocrine and secretory organ, releasing a wide range of protein factors and signals termed adipokines - in addition to fatty acids and other lipid moieties. A paradigm shift came with the discovery of leptin, a pleiotropic hormone which is a critical signal to the hypothalamus in the control of appetite and energy balance. A number of adipokines, including adiponectin, tumour necrosis factor-alpha, interleukin (IL)-1beta, IL-6, IL-8, IL-10, monocyte chemoattractant protein-1, macrophage migration inhibitory factor, nerve growth factor, vascular endothelial growth factor, plasminogen activator inhibitor-1 and haptoglobin, are linked to inflammation and the inflammatory response. Obesity is characterized by a state of mild inflammation, and the expression and release of inflammation-related adipokines generally rises as adipose tissue expands; a notable exception is adiponectin, with its anti-inflammatory action, the levels of which fall. WAT may be the main site of inflammation in obesity, increased circulating levels of inflammatory markers reflecting spillover from an 'inflamed' tissue, leading to the obesity-associated pathologies of type 2 diabetes and the metabolic syndrome. From the wide range of adipokines now identified, it is evident that WAT is highly integrated into overall physiological regulation, involving extensive crosstalk with other organs and multiple metabolic systems. Whether major changes in adipokine production in obesity, particularly of those factors linked to inflammation, are unique to this condition, or are a feature of all situations in which there are substantial increases in adipose mass (such as pregnancy, and pre-hibernatory and pre-migratory fattening) requires consideration.
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PMID:Endocrine and signalling role of adipose tissue: new perspectives on fat. 1602 20

The aim of this study was to investigate the relationship of Interleukin-8 (IL-8) with vascular endothelial growth factor (VEGF) and plasminogen activator system (PA system) in the progression of colorectal cancer (CRC). In eighty-seven patients with CRC, the levels of IL-8, and VEGF as representative angiogenic factors and urokinase-type plasminogen activator (uPA), uPA receptor (uPAR), plasminogen activator inhibitor-1 (PAI-1), and PAI-2 as representative invasive factors were quantitatively assayed in tumor and adjacent normal tissues. The levels of IL-8, VEGF, and PA system factors in tumor tissues were all significantly higher than those in normal tissues. The IL-8 level was significantly associated with tumor size, depth of infiltration, Dukes stage, and liver metastasis, and also significantly correlated with the levels of VEGF, uPAR, uPA, and PAI-1. The VEGF level was significantly associated with tumor size, vascular involvement. The levels of uPAR and PAI-1 were significantly associated with tumor size and depth of infiltration, and the uPAR level was associated with liver metastasis. The VEGF level was significantly correlated with the levels of uPAR and PAI-1. These results reveal that IL-8, VEGF, and PA system factors are contributed to tumor growth, invasion, and metastasis in CRC. Univariate analysis revealed that high levels of IL-8, VEGF, and uPAR were significantly associated with a shorter overall survival time; however, multivariate analysis identified only liver metastasis as an independent prognostic factor. In conclusion, IL-8 is responsible to tumor progression and liver metastasis of CRC, and the activation of PAS induced by IL-8 as well as VEGF may play an important role in the progression of CRC.
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PMID:Association of interleukin-8 and plasminogen activator system in the progression of colorectal cancer. 1608 82

Thiazolidinediones (TZDs) are selective ligands of peroxisome-proliferator-activated receptor gamma increasingly used in the treatment of type 2 diabetes. Both in vitro and in vivo studies provide evidence that TZDs have anti-inflammatory properties. TZDs inhibit macrophage activation and decrease inflammatory cytokine expression and release in macrophage and monocyte. In vivo, treatment with TZDs decreases circulating mononuclear cells nuclear NF-kB content while increasing, in the same cells, expression of IkB, an NK-kB inhibitor. Furthermore, TZD treatment results in decreased plasma levels of inflammation and cardiovascular risk markers such as CRP, MMP9, PAI-1 and sCD40 in both obese and type 2 diabetic patients. Finally, TZDs induce synoviocyte apoptosis and reduce secretion of TNFalpha, IL-6 and IL-8 in synoviocyte from rheumatoid arthritis patients. TZDs might thus be considered for use in clinical trials targeting prevention of atherosclerosis and cardiovascular diseases and in pilot trials exploring the possibility that TZDs might help in the treatment of rheumatic diseases.
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PMID:Thiazolidinediones and inflammation. 1621 90

Insulin resistance has been implicated as one possible factor that links visceral obesity to unfavourable metabolic and cardiovascular consequences. However, the mechanism whereby adipose tissue causes alterations in insulin action remains unclear. White adipose tissue is secreting several hormones, particularly leptin and adiponectin, and a variety of other protein signals: the adipocytokines. They include proteins involved in the regulation of energy balance, lipid and glucose metabolism as well as angiogenesis, vascular and blood pressure regulation. Visceral obesity and inflammation within white adipose tissue may be a crucial step contributing to the emergence of insulin resistance, type 2 diabetes and atherosclerosis. A growing list of adipocytokines involved in inflammation (IL-1beta, IL-6, IL-8, IL-10, TNF-alpha, TGF-beta,) and the acute-phase response (serum amyloid A, PAI-1) have been found to be increased in the metabolic syndrome. It is, however, unclear as to the extent adipose tissue contributes quantitatively to the elevated circulating levels of these factors in obesity and how they may affect the insulin-dependent tissues. This review describes the role of the currently known adipocytokines and hormones released by adipose tissue in generating the insulin resistance state and the chronic inflammatory profile which frequently goes together with visceral obesity.
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PMID:Review article: adipocytokines and insulin resistance. 1622 63

Adipose tissue is responsive to both central and peripheral metabolic signals and is itself capable of secreting a number of proteins. These adipocyte-specific or enriched proteins, termed adipokines, have been shown to have a variety of local, peripheral, and central effects. These secreted proteins, which include tumor necrosis factor (TNF)-alpha, resistin, IL-6, IL-8, acylation-stimulating protein (ASP), angiotensinogen, plasminogen activator inhibitor-1 (PAI-1) ("bad" adipokines) and leptin, adiponectin ("good" adipokines) seem to play important regulatory roles in a variety of complex processes, including fat metabolism, feeding behavior, hemostasis, vascular tone, energy balance, and insulin sensitivity, but none is without controversy regarding its respective mechanism and scope of action. The present review is focused on the effects of free fatty acids and a restricted number of adipokines, which have been implicated in vascular (angiotensinogen, PAI-1) and energy and glucose homeostasis (ASP, TNFalpha, IL-6, resistin, leptin, adiponectin).
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PMID:Adipocyte-derived hormones, cytokines, and mediators. 1662 95


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