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)

Hyperglycemia is the major cause of diabetic angiopathy. Aim of our study was to evaluate the impact of high glucose on cell growth and function of human "diabetic" endothelial cells (EC). Incubation of non-diabetic EC with glucose moderately inhibited cell growth and increased the expression of ICAM-1 and E-selectin. In the disease-specific EC, glucose treatment resulted also in moderately inhibited cell growth by 5-10%, increased basal expression of VCAM-1 by 10-20%, and an enhanced release of monocyte-chemoattractant-protein-1 (MCP-1) by 40-70%. The expression of ICAM-1 and E-selectin and the release of IL-6 and IL-8 was not affected. The usage of our disease-specific EC model might evaluate the impact of systemic factors of diabetic patients in the progression of endothelial dysfunction, and may be suitable to develop relevant therapeutic regimens.
 ...
PMID:Hyperglycemia increases the levels of vascular cellular adhesion molecule-1 and monocyte-chemoattractant-protein-1 in the diabetic endothelial cell. 1761 4

Hyperglycemia causes direct neuronal damage in diabetic encephalopathy. Microglia have been found to be activated in diabetic encephalopathy, presumably mediating and amplifying neuron degeneration. Chemokine IL-8 plays an important role in the pathogenesis of encephalopathy. Therefore, we investigated whether high glucose could activate microglia and stimulate IL-8 secretion and if so, the possible mechanisms that were involved. ELISA results showed that treatment with high glucose (35 mM) compared with treatment with low glucose (10 mM) time-dependently elevated secretion of GRO (the rat ortholog of human IL-8) in primary cultured rat microglia. Real-time PCR results showed GRO mRNA expression also increased in response to high glucose in a time-dependent manner. These effects were specific to high glucose because the osmolality control had no such effect. High-glucose treatment stimulated the formation of ROS, as seen in the DCF fluorescence assay, increased phosphorylation of PKC, as seen in the Western blot analysis, and activated NF-kappaB, as seen in the luciferase reporter assay. In addition, treatment with the ROS scavenger NAC (2 mM) significantly reduced the high glucose-induced phosphorylation of PKC and GRO secretion. Treatment with the PKC activator PMA (10-50 nM) stimulated GRO secretion, and the PKC inhibitors calphostin C (300 nM) or chelerythrine (1 microM) attenuated the high glucose-induced GRO secretion. Furthermore, the NF-kappaB inhibitors MG132 (10 microM) or PDTC (5 microM) completely blocked the high glucose-induced GRO secretion. In conclusion, high glucose induces GRO secretion and mRNA expression in activated rat microglia, which is mediated by the ROS, PKC, and NF-kappaB pathways. High glucose-induced IL-8 production by microglia may contribute to diabetic encephalopathy.
 ...
PMID:High glucose stimulates GRO secretion from rat microglia via ROS, PKC, and NF-kappaB pathways. 1763 99

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.
 ...
PMID:Unchanged asymmetric dimethylarginine levels in non-diabetic, premenopausal obese women who have common risk factors for cardiovascular disease. 1787 18

Obstructive sleep apnea (OSA), often concomitant with obesity, increases the risk for the metabolic syndrome. One mechanism that may participate in this association is upregulation of inflammatory pathways. We used structural equation modeling to assess the interrelations between childhood obesity, OSA, inflammation, and metabolic dysfunction. One hundred and eighty-four children (127 boys, mean age: 8.5 +/- 4.1 years) had height and weight measured, underwent overnight polysomnography and had fasting blood taken. The blood was analyzed for insulin, glucose, lipids, leptin, and cytokines [interferon (IFN)-gamma, granulocyte macrophage-colony stimulating factor, interleukin (IL)-1beta, IL-2, IL-4, IL-6, IL-8, IL-10, IL-12, tumor necrosis factor-alpha]. Structural equation modeling (SEM) was used to evaluate associations between the outcomes of interest including hypoxia, arousal (related to respiratory and spontaneous), obesity, metabolic dysfunction, and inflammatory markers. Two cytokine factors and one metabolic factor were derived for the SEM. These factors provided good fit in the structural equation model (chi(2)/df = 2.855; comparative fit index = 0.90, root mean squared error of approximation = 0.10) and all factor loadings were significantly different from zero (P < or = 0.01). Overall, our results indicate that while obesity (as measured by body mass index z-score) has a major influence on the metabolic dysfunction associated with OSA, arousal indices, and cytokine markers may also influence this association. Our results support the hypothesis that OSA is a contributor to the mechanisms that link sleep, systemic inflammation and insulin resistance, and show that the interrelations may begin in childhood.
 ...
PMID:Structural equation modeling of sleep apnea, inflammation, and metabolic dysfunction in children. 1803 84

Skeletal muscle fibers express several cytokines, including interleukin (IL)-6, IL-8, and IL-15. Solid evidence exists that muscular IL-6 and IL-8 are regulated by muscle contractions, at both the mRNA and the protein levels. IL-6 increases insulin-stimulated glucose disposal and fatty acid oxidation in humans in vivo. Both IL-6 and IL-8 are released from working skeletal muscle, but because IL-6 contributes to the systemic circulation only a small transient net release of IL-8 is found from working muscle, suggesting that IL-8 may exert its effects locally in the muscle. IL-15 is a recently discovered growth factor, which is highly expressed in skeletal muscle. Interestingly, although IL-15 has been demonstrated as having anabolic effects on skeletal muscle in vitro and in vivo, it seems to play a role in reducing adipose tissue mass, and a role for IL-15 in muscle-fat cross-talk has been hypothesized. In conclusion, muscle-derived cytokines appear to have important roles in metabolism, and exercise plays a role in orchestrating the interplay between cytokines and metabolism.
 ...
PMID:The biological roles of exercise-induced cytokines: IL-6, IL-8, and IL-15. 1805 6

Adipose tissue-derived cytokines are presumably involved in obesity-associated pathologies including type 2 diabetes and atherosclerosis. Here we studied the lipopolysaccharide (LPS)-induced expression dynamics of tumor necrosis factor-alpha (TNFalpha), interleukin-6 (IL-6), IL-8 and IL-10 in human adipose tissue biopsies, in preadipocyte-derived adipocytes, and in mesenchymal stem cell (MSC)-derived adipocytes. TNFalpha, IL-6, IL-8 and IL-10 secretions by adipose tissue explants were increased 5.5-, 19.5-, 3.5- and 12.5-fold, respectively, by LPS (1 microg/mL) administration. Concordantly, IL-6 and IL-8 release was dose-dependently induced in MSC-derived adipocytes by LPS (>10 pg/mL). In contrast, TNFalpha and IL-10 remained undetectable even at the highest LPS dose (1 microg/mL) after 24h. In MSC- and preadipocyte-derived adipocytes, respectively, exposure to LPS evoked a weak and transient induction of TNFalpha mRNA whereas induction of IL-6 and IL-8 mRNA were pronounced and sustained for at least 24h. Basal glucose uptake, lipolysis and IL-6 mRNA were induced by exogenous TNFalpha (10 ng/mL) but not by IL-6 (10 ng/mL), IL-8 (100 ng/mL) and IL-10 (20 ng/mL). In this adipocyte model TNFalpha induces well known metabolic effects, but together with previous reports these data suggest that inflammation-induced TNFalpha may derive from non-adipocyte sources in adipose tissue, likely to be macrophages.
 ...
PMID:LPS induces interleukin-6 and interleukin-8 but not tumor necrosis factor-alpha in human adipocytes. 1806 Aug 2

Inflammation is associated with obesity, the metabolic syndrome, and diabetes. No data are available on the effect of weight reduction on the gene expression of cytokines in immune cells in obesity and the metabolic syndrome. We assessed how long-term weight loss affects expression of cytokines in peripheral blood mononuclear cells (PBMCs) in individuals with impaired glucose metabolism and the metabolic syndrome. Data from 34 subjects randomized to either a weight reduction or a control group for a 33-week period were analyzed. The messenger RNA (mRNA) expression of interleukins (ILs) in PBMCs was measured using real-time polymerase chain reaction. Measures of insulin and glucose metabolism (intravenous and oral glucose tolerance tests), body composition, and circulating adipokines and inflammatory markers were also assessed. Weight reduction resulted in a decrease in the mRNA expression of IL-1beta (IL1B), IL-1 receptor antagonist, and tumor necrosis factor alpha (P < .001) and an increase in expression of IL-6 (IL6) and IL-8 (P < .01). The increase in IL6 expression was associated with a decrease in fasting glycemia (r = -0.53, P < .01). Interestingly, the decrease in IL1B expression was correlated with an increase in insulin sensitivity index (r = -0.68, P < .01). In general, a decrease in circulating levels of adipokines and inflammatory markers was also observed after weight loss. Weight loss altered gene expression of cytokines related to inflammation and the immune response in PBMCs. Changes in IL6 mRNA expression were associated with changes in fasting glycemia. The decrease in IL-1 receptor antagonist expression after weight loss and the strong correlation between the decrease in IL1B expression and the increase in insulin sensitivity suggest a contribution of these genes to insulin-resistant states found in obesity and the metabolic syndrome.
 ...
PMID:Effect of weight loss on cytokine messenger RNA expression in peripheral blood mononuclear cells of obese subjects with the metabolic syndrome. 1819 Oct 48

The impressive correlation between cardiovascular disease and alterations in glucose metabolism has raised the likelihood that atherosclerosis and type 2 diabetes may share common antecedents. Inflammation is emerging as a conceivable etiologic mechanism for both. Interleukins are regulatory proteins with ability to accelerate or inhibit inflammatory processes, and matrixins are prepro enzymes responsible for the timely breakdown of extracellular matrix. Interleukins (ILs) are classified based on their role in diabetes and atherosclerosis, hypothesizing that each interleukin acts on both diseases in the same direction - regardless if harmful, favorable or neutral. They are clustered into three groups: noxious (the 'bad', 8 members), comprising IL-1, IL-2, IL-6, IL-7, IL-8, IL-15, IL-17 and IL-18; protective (the 'good', 5 members), comprising IL-4, IL-10, IL-11, IL-12 and IL-13; and 'aloof' , comprising IL-5, IL-9, IL-14, IL-16 and IL-19 through IL-29 (15 members). Each group presented converging effects on both diseases. IL-3 was reluctant to clustering and IL-30 through 33 were not included due to the scarce available data. It may be seen that (1) favorable effects of a given interleukin on either diabetes or atherosclerosis predicts similar effects on the other; (2) equally, harmful interleukin effects on one disease can be extrapolated to the other, and (3) absence of influence of a given interleukin on one of these diseases forecasts lack of effects on the other. Matrixins seem to present a similar pathophysiological pattern. These facts further support the unifying etiologic theory of diabetes and heart disease, emphasizing the importance of a cardiovascular diabetologic approach to these cytokines for future research. A pharmacologic simultaneous targeting of interleukins and matrixins might provide an effective means to concurrently control both atherosclerosis and diabetes.
 ...
PMID:Biomarkers in cardiovascular diabetology: interleukins and matrixins. 1823 Sep 55

Factors that upregulate the inflammatory status of islets probably contribute to detrimental processes leading to islet loss and impaired post-transplant function. Glucocorticoids have the potential to counteract inflammation and thus improve islet quality and function. However, glucocorticoids have diabetogenic properties and are known to hamper islet function in vivo. We examined the effect of glucocorticoids on human islets in vitro and in vivo after 48 h of exposure to different concentrations of methylprednisolone. Protein and/or mRNA levels of insulin, interleukin (IL)-8, macrophage chemoattractant protein (MCP)-1, tissue factor (TF), and IL-10 were assessed by enzyme immunosorbent assay and real time quantitative reverse transcription-polymerase chain reaction. Viability was assessed with fluorescein diacetate-propidium iodide staining, adenosine triphosphate (ATP) content and caspase activity. Six-hundred islet equivalents (IEQ) were transplanted to severe combined immunodeficiency disease mice and graft function assessed by glucose measurements and intraperitoneal glucose tolerance tests. Glucocorticoids reduce mRNA and protein levels of TF, MCP-1 and IL-8, and enhance ATP content. Insulin secretion was initially inhibited; however, after 7 days in culture, it was superior to controls. Islets exposed to methylprednisolone cured diabetic mice more effectively than control islets. In conclusion, glucocorticoids have potent anti-inflammatory properties on human islets without permanent effects on insulin metabolism. Brief glucocorticoid exposure improves function of transplanted human islets in vivo.
 ...
PMID:Glucocorticoids reduce pro-inflammatory cytokines and tissue factor in vitro and improve function of transplanted human islets in vivo. 1834 12

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.
 ...
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


<< Previous 1 2 3 4 5 6 7 8 9 10 Next >>