Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UNIPROT:P10145 (IL-8)
 23,849 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Several recently published reports, including ours, suggest that adiponectin is a strong proinflammatory agent. Indeed, exposure of human placenta and adipose tissue to adiponectin induces the production of interleukin-1beta (IL-1beta), IL-6, tumor necrosis factor alpha (TNF-alpha), and prostaglandin E2 (PGE2). We have previously shown that adiponectin is a powerful inducer of proinflammatory cytokines production by macrophages. The reported anti-inflammatory effect of adiponectin may be due to the induction of macrophage tolerance to further adiponectin exposure or to other proinflammatory stimuli including the Toll-like receptor (TLR) 3 ligand polyI:C and the TLR4 ligand lipopolysaccharide (LPS). We now present additional data supporting the hypothesis that adiponectin is a strong proinflammatory adipokine. More specifically, we demonstrate that adiponectin induces IL-1beta and IL-8 from THP-1 macrophage cell line. The effect of adiponectin is not restricted to differentiated THP-1 macrophages but it is evident at lower levels in undifferentiated THP-1 monocytes promoting TNF-alpha, IL-6, and IL-8 production. Thus, its high levels in the circulation of lean subjects render their macrophages resistant to several proinflammatory stimuli including its own thus acting in effect as an anti-inflammatory agent. Lowering of its high levels, as a consequence of increased body mass index (BMI), renders macrophages sensitive to any proinflammatory insult.
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PMID:Peripheral factors in the metabolic syndrome: the pivotal role of adiponectin. 1714 40

Trans-fatty acid intake is associated with an increased risk of CHD and diabetes. The effects of single trans-fatty acid isomers are largely unexplored. The present study examined the effects of a 6-week supplementation with two trans-18 : 1 isomers (trans-11 and trans-12) in human subjects on immune cells, several inflammatory and immunological biomarkers (for example, IL, TNFalpha, C-reactive protein, adiponectin, intercellular adhesion molecule-1, prostacyclin, phagocytic process). Following a 2-week adaptation period without supplements, the test group (n 12) received vaccenic acid (trans-11-18:1) and trans-12-18 : 1 in equal amounts (6.0 g/d) for 6 weeks. The control group (n 12) consumed an oil without trans-fatty acids and conjugated linoleic acids (CLA). Samples were collected at the end of both periods. Trans-11- and trans-12-18 : 1 were significantly increased in cellular lipids. The endogenous synthesis of cis-9, trans-11-CLA from trans-11-18 : 1 was demonstrated via increased CLA in cellular lipids of the test group. Generally, trans-isomer supplementation did not affect either inflammatory biomarkers (for example, IL-6, IL-8, TNFalpha) or immune function (for example, phagocytosis) during the present study. The dietary supplementation of trans-11- and trans-12-18 : 1 (6 g/d) and their accumulation in leucocytes had no effects on biomarkers of inflammation and immune function. However, because of the limited data on the safety of trans-fatty acid intake and effects of individual trans isomers on human health (for example, trans-9-18 : 1, trans-10-18 : 1) at present, it is prudent to reduce trans-fat intake in general.
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PMID:Dietary supplementation with trans-11- and trans-12-18 : 1 increases cis-9, trans-11-conjugated linoleic acid in human immune cells, but without effects on biomarkers of immune function and inflammation. 1736 66

Cytokine-induced inflammation is involved in the pathogenesis of type 2 diabetes mellitus (DM). We investigated plasma concentrations and ex vivo production of cytokines and chemokines, and intracellular signalling molecules, mitogen-activated protein kinases (MAPK) in T helper (Th) cells and monocytes in 94 type 2 diabetic patients with or without nephropathy and 20 healthy controls. Plasma concentrations of inflammatory cytokines tumour necrosis factor (TNF)-alpha, interleukin (IL)-6, IL-18 and chemokine CCL2 in patients with diabetic nephropathy (DN) were significantly higher than control subjects, while IL-10, CXCL8, CXCL9, CXCL10 and adiponectin concentrations of DN were significantly higher than patients without diabetic nephropathy (NDN) and control subjects (all P < 0.05). Plasma concentrations of TNF-alpha, IL-6, IL-10, IL-18, CCL2, CXCL8, CXCL9, CXCL10 and adiponectin exhibited significant positive correlation with urine albumin : creatinine ratio in DN patients. The percentage increases of ex vivo production of IL-6, CXCL8, CXCL10, CCL2 and CCL5 upon TNF-alpha activation were significantly higher in both NDN and DN patients than controls (all P < 0.05). The percentage increases in IL-18-induced phosphorylation of extracellular signal-regulated kinase (ERK) in Th cells of NDN and DN were significantly higher than controls (P < 0.05), while the percentage increase in TNF-alpha-induced phosphorylation of p38 MAPK in monocytes and IL-18-induced phosphorylation of p38 MAPK in Th cells and monocytes were significantly higher in NDN patients than controls. These results confirmed that the aberrant production of inflammatory cytokines and chemokines and differential activation of MAPK in different leucocytes are the underlying immunopathological mechanisms of type 2 DM patients with DN.
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PMID:Aberrant activation profile of cytokines and mitogen-activated protein kinases in type 2 diabetic patients with nephropathy. 1742 53

Migraine is a common disorder, characterized by recurrent episodes of headache and associated symptoms. The full pathophysiology of migraine is incompletely delineated. Current theories suggest that it is a neurovascular disorder involving cortical depression, neurogenic inflammation and vasodilation. Various neuropeptides and cytokines have been implicated in the pathophysiology of migraine including calcitonin gene-related peptide, interleukin (IL)-1, IL-6 and tumour necrosis factor (TNF)-alpha. There is evidence demonstrating an association between migraine and processes associated with inflammation, atherosclerosis, immunity and insulin sensitivity. Similarly, adiponectin, an adipocytokine secreted by adipose tissue, has protective roles against the development of insulin resistance, dyslipidaemia and atherosclerosis and exhibits anti-inflammatory properties. The anti-inflammatory activities of adiponectin include inhibition of IL-6 and TNF-induced IL-8 formation, as well as induction of the anti-inflammatory cytokines IL-10 and IL-1 receptor antagonist. Adiponectin levels are also inversely correlated with C-reactive protein (CRP), TNF-alpha and IL-6 levels. Likewise, recent studies have shown a possible correlation between CRP, TNF-alpha and IL-6 and migraine attacks. In addition, insulin sensitivity is impaired in migraine and obesity is a risk factor for the transformation from episodic to chronic migraine. In this review we discuss the basic science of adiponectin and its potential connection to the pathophysiology of migraine. Future research may focus on how adiponectin levels are potentially altered during migraine attacks, and how that information can be potentially translated into migraine therapy.
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PMID:Migraine and adiponectin: is there a connection? 1744 81

The metabolic syndrome is associated with a dysregulated adipose tissue; in part a consequence of adipose cell enlargement and the associated infiltration of macrophages. Adipose cell enlargement leads to a proinflammatory state in the cells with reduced secretion of adiponectin and with increased secretion of several cytokines and chemokines including interleukin (IL)-6, IL-8, and MCP-1. MCP-1 has been shown to play an important role for the associated recruitment of macrophages into the adipose tissue. The increased release of cytokines leads to an impaired differentiation of the preadipocytes with reduced lipid accumulation and induction of adiponectin, thus promoting ectopic lipid storage. In particular tumor necrosis factor (TNF) alpha, but also IL-6, has been shown to induce these effects in preadipocytes and this is associated with an increased Wnt signaling maintaining the cells in an undifferentiated and proinflammatory state. The proinflammatory state in the adipose tissue also leads to a local insulin resistance including an impaired inhibitory effect of insulin on FFA release. The insulin resistance further supports the proinflammatory state because insulin, by itself, is both antilipolytic and antiinflammatory by antagonizing cytokine-induced activation of STAT signaling.
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PMID:Inflamed adipose tissue: a culprit underlying the metabolic syndrome and atherosclerosis. 1790 71

This study was performed to test whether plasma asymmetric dimethylarginine (ADMA) concentrations are related to obesity and obesity complications including decrement in insulin sensitivity and adiponectin levels, dyslipidemia and low-grade inflammation. Asymmetric dimethylarginine (ADMA) and symmetric dimethylarginine (SDMA) concentrations were analyzed by HPLC in 17 overweight (BMI > or = 25 kg/m2) and 40 obese (BMI > or = 30 kg/m2) premenopausal women. Age-matched healthy women were studied as controls. Obesity did not give rise to a significant change in circulating ADMA levels but reduced in SDMA levels. As compared with control subjects (0.441 +/- 0.102 microM), ADMA values in overweight and obese subjects were found to be as 0.412 +/- 0.102 and 0.436 +/- 0.093, respectively. No Pearson's association of ADMA with relevant risk variables for cardiovascular disease, including blood pressure, insulin sensitivity, inflammatory markers, lipid and adiponectin levels. However, in linear regression analysis, BMI, diastolic blood pressure, glucose, insulin, and IL-8 emerged as significant predictors of ADMA. In spite of obese women have elevated hs-CRP, triglyceride levels and decreased insulin sensitivity, adiponectin and HDL-cholesterol levels, all of which is closely linked risk factors for cardiovascular disease, circulating ADMA levels remained unchanged in obese individuals as compared with controls.
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PMID:Unchanged asymmetric dimethylarginine levels in non-diabetic, premenopausal obese women who have common risk factors for cardiovascular disease. 1787 18

Adipokines, soluble mediators produced by adipocytes, may link adipose tissue to the inflammatory, metabolic, and immune dysregulation that characterize many obesity-related diseases. The stability of plasma adipokine levels within individuals, their seasonal variability, intercorrelations, and relationships to well-established measures of adiposity are incompletely defined. We measured levels of 12 adipokines [interleukin 1beta (IL-1beta), IL-6, IL-8, tumor necrosis factor-alpha (TNF-alpha), plasminogen activator inhibitor-1 (PAI-1), high-sensitivity C-reactive protein (hsCRP), monocyte chemoattractant protein-1 (MCP-1), nerve growth factor (NGF), leptin, adiponectin, hepatocyte growth factor (HGF), and resistin] in four seasonal random plasma samples of 48 male participants of a population-based cohort study. The representativeness of single measurements was assessed by correlating the adipokine levels of a single, random sample with the mean levels from the remaining three samples using a bootstrap approach and using intra-class correlation coefficients (ICC). Spearman correlations between adipokine levels, age, body mass index (BMI), and waist-to-hip ratio (WHR) were estimated. Correlations between plasma adipokine levels from one random sample and the mean of the remaining three seasonal samples ranged from 0.57 to 0.89. Over the 1-year study period, the ICCs for adipokine levels ranged from 0.44 (PAI-1) to 0.83 (HGF). IL-8, MCP-1, and resistin levels were positively associated with age; HGF and PAI-1 levels were correlated with BMI and WHR. This study suggests that adipokine levels in a single blood sample may be useful biomarkers of inflammation in population-based studies of obesity-related disease.
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PMID:Intra-individual variation of plasma adipokine levels and utility of single measurement of these biomarkers in population-based studies. 1800 38

Low-glycemic index (GI) foods and foods rich in whole grain are associated with reduced risk of type 2 diabetes and cardiovascular disease. We studied the effect of cereal-based bread evening meals (50 g available starch), varying in GI and content of indigestible carbohydrates, on glucose tolerance and related variables after a subsequent standardized breakfast in healthy subjects (n = 15). At breakfast, blood was sampled for 3 h for analysis of blood glucose, serum insulin, serum FFA, serum triacylglycerides, plasma glucagon, plasma gastric-inhibitory peptide, plasma glucagon-like peptide-1 (GLP-1), serum interleukin (IL)-6, serum IL-8, and plasma adiponectin. Satiety was subjectively rated after breakfast and the gastric emptying rate (GER) was determined using paracetamol as a marker. Breath hydrogen was measured as an indicator of colonic fermentation. Evening meals with barley kernel based bread (ordinary, high-amylose- or beta-glucan-rich genotypes) or an evening meal with white wheat flour bread (WWB) enriched with a mixture of barley fiber and resistant starch improved glucose tolerance at the subsequent breakfast compared with unsupplemented WWB (P < 0.05). At breakfast, the glucose response was inversely correlated with colonic fermentation (r = -0.25; P < 0.05) and GLP-1 (r = -0.26; P < 0.05) and positively correlated with FFA (r = 0.37; P < 0.001). IL-6 was lower (P < 0.01) and adiponectin was higher (P < 0.05) at breakfast following an evening meal with barley-kernel bread compared with WWB. Breath hydrogen correlated positively with satiety (r = 0.27; P < 0.01) and inversely with GER (r = -0.23; P < 0.05). In conclusion, the composition of indigestible carbohydrates of the evening meal may affect glycemic excursions and related metabolic risk variables at breakfast through a mechanism involving colonic fermentation. The results provide evidence for a link between gut microbial metabolism and key factors associated with insulin resistance.
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PMID:Including indigestible carbohydrates in the evening meal of healthy subjects improves glucose tolerance, lowers inflammatory markers, and increases satiety after a subsequent standardized breakfast. 1835 28

The abundance of the adiponectin receptors, AdipoR1 and AdipoR2, and the effects of the antidiabetic adipokine adiponectin in monocytes of normal-weight and overweight controls and type 2 diabetic patients (T2D) were analyzed. AdipoR1 and AdipoR2 mRNAs were increased in monocytes of obese controls and T2D patients when compared to normal-weight controls, and AdipoR1 mRNA positively correlated to AdipoR2 mRNA, the waist to hip ratio and systemic adiponectin. However, AdipoR1 and AdipoR2 proteins were lower in monocytes of T2D compared to normal-weight donors. Induction of IL-6 and IL-8 by adiponectin, an effect involving p38 MAPK, was also reduced in T2D monocytes.
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PMID:Reduced response to adiponectin and lower abundance of adiponectin receptor proteins in type 2 diabetic monocytes. 1844 81

Chronic infection with hepatitis C virus (HCV) can induce insulin resistance (IR) in a genotype-dependent fashion, thus contributing to steatosis, progression of fibrosis and resistance to interferon therapy. The molecular mechanisms in genotype 1 patients that lead to metabolic syndrome are still ambiguous. Based on our current understanding, HCV proteins associate with mitochondria and endoplasmic reticulum and promote oxidative stress. The latter mediates signals involving the p38 mitogen-activated protein kinase and activates nuclear factor kappa B. This transcription factor plays a key role in the expression of cytokines, tumor necrosis factor alpha (TNF-alpha), interleukin 6, interleukin 8, tumor growth factor beta, and Fas ligand. TNF-alpha inhibits the function of insulin receptor substrates and decreases the expression of the glucose transporter and lipoprotein lipase in peripheral tissues, which is responsible for the promotion of insulin resistance. Furthermore, reduced adiponectin levels, loss of adiponectin receptors, and decreased anti-inflammatory peroxisome proliferator-activated receptor alpha in the liver of HCV patients may contribute to reduced fatty acid oxidation, inflammation, and eventually lipotoxicity. This chain of events may be initiated by HCV-associated IR and provides a direction for future research in the areas of therapeutic intervention.
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PMID:Hepatitis C virus infection: molecular pathways to metabolic syndrome. 1875 83


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