interleukin-8 and Dyslipidemias

Hypercholesterolaemia is associated with increased plasma levels of vascular endothelial growth factor (VEGF) and interleukin-8 (IL-8). We studied the effect of rosuvastatin monotherapy or its combination at a lower dose with omega-3 polyunsaturated fatty acids (ω-3 PUFAs) in the VEGF and IL-8 plasma levels in patients with mixed dyslipidaemia.. Fifty patients with mixed dyslipidaemia were recruited. Fifty-five normolipidaemic, apparently healthy, ageand sex- matched subjects acted as controls. Patients were randomized to 40 mg/day rosuvastatin (R group, n=26) or 10 mg/day rosuvastatin plus 2 g/day of ω-3 PUFAs (R+O group, n=24). The levels of VEGF and IL-8 in plasma, were assessed at baseline and 3 months post-treatment.. At baseline, both plasma VEGF and IL-8 levels were significantly higher in the R and R+O groups compared with controls (p<0.04, p<0.03 and p<0.02, p<0.03, respectively). Post-treatment levels of VEGF were decreased in the R group while a significant increase was observed in the R+O group, compared with baseline levels (p<0.02 and p<0.03, respectively). Post-treatment IL-8 levels were decreased in both R and R+O groups (p<0.03 and p<0.04, respectively).. We show for the first time that either rosuvastatin monotherapy or its combination at a lower dose with ω-3 PUFAs reduces IL-8 levels in mixed dyslipidaemic patients. High-dose rosuvastatin monotherapy reduces VEGF values, whereas a significant increase is observed in patients receiving lower dose rosuvastatin with ω-3 PUFAs. The clinical significance of the above findings regarding cardiovascular risk remains to be established.

Topics: Adult; Aged; Biomarkers; Docosahexaenoic Acids; Drug Combinations; Drug Therapy, Combination; Dyslipidemias; Eicosapentaenoic Acid; Female; Greece; Humans; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Interleukin-8; Lipids; Male; Middle Aged; Pilot Projects; Rosuvastatin Calcium; Time Factors; Treatment Outcome; Vascular Endothelial Growth Factor A

Childhood obesity is a global and increasing health issue. Inflammation and dysregulated adipose tissue secretion are common findings in obesity and have been related to poor metabolic function. Given that DNA methylation impacts gene expression and is responsive to environmental changes, we aimed, in addition to characterize the patients in anthropometric and biochemical terms, to determine the expression of cytokines and adipokines, assess the methylation on regulatory regions of the genes that code for these molecules, and investigate the association of the expression and gene methylation with anthropometric and biochemical parameters in childhood obesity. Obese children present dyslipidemia, dysregulated serum levels of adipokines and their ratios, altered leukocytic expression of cytokines, and higher methylation at the CXCL8 promoter as compared to the control group. However, no significant results were observed in the fasting plasma glucose levels or the methylation of TGFB1, LEP, and the enhancer region of ADIPOQ. We also found negative correlations of CXCL8 expression with anthropometric and biochemical parameters, and positive correlation of CXCL8 promoter methylation and the serum levels of hepatic enzymes. Our results indicate that changes in metabolic parameters observed in childhood obesity are associated with the expression of adipokines and cytokines, and the methylation status at the CXCL8 promoter. CXCL8 may be a key factor for these alterations, as it correlates with many of the parameters assessed in the present study.

Topics: Adipokines; Adiponectin; Anthropometry; C-Reactive Protein; Child; DNA Methylation; Dyslipidemias; Female; Humans; Interleukin-8; Leptin; Liver; Male; Pediatric Obesity; Promoter Regions, Genetic

Engineered zinc oxide nanoparticles (ZnO-NPs) are currently being produced in high tonnage. Exposure to ZnO-NPs presents potential risks to cardiovascular system. Thus far, the toxicological effects of ZnO-NPs on cardiovascular system have not been well characterized. In this study, human coronary artery endothelial cells (HCAECs) were exposed to ZnO-NPs directly or indirectly using a transwell coculture system with human alveolar epithelial cell line A549 to mimic the lung/circulation interaction. It was shown that levels of proinflammatory mediators (interleukin-8 [IL-8] and tumor necrosis factor-α [TNF-α]) and biomarkers of atherosclerogenesis (heme oxygenase-1 [HO-1] and platelet endothelial cell adhesion molecules-1 [PECAM-1]) in the supernatants of culture media were significantly increased. Pretreatment of A549 cells on the apical side of the coculture system with the phagocytosis inhibitor cytochalasin B (CB) blocked ZnO-NP-induced HO-1 and PECAM-1 expression in HCAEC, indicating that endocytosis of ZnO-NPs by alveolar epithelial cells was involved in ZnO-NP-induced HO-1 or PECAM-1 expression in endothelial cells. Moreover, Wistar rats were intratracheally instilled with ZnO-NP suspension and high fat diet (positive control). ZnO-NP treatment induced lung and systemic inflammation, dyslipidemia, increased levels of serum HO-1 and PECAM-1, and aortic pathological damage. Taken together, exposure to ZnO-NPs could induce atherosclerotic alterations, which might involve phagocytosis of nanoparticles and inflammation in the lung.

Topics: Animals; Atherosclerosis; Coculture Techniques; Coronary Vessels; Dyslipidemias; Endocytosis; Endothelial Cells; Endothelium, Vascular; Heme Oxygenase-1; Humans; Interleukin-8; Lung; Male; Nanoparticles; Phagocytosis; Platelet Endothelial Cell Adhesion Molecule-1; Rats, Wistar; Tumor Necrosis Factor-alpha; Zinc Oxide

Psoriasis is a chronic inflammatory skin disease characterized by altered proliferation and differentiation of keratinocytes as well as infiltration of immune cells. Increased expression of Th17 cells and cytokines secreted by them provides evidence for its central role in the pathogenesis of psoriasis. IL-17A, signature cytokine of Th17 cells was found to be highly differentially expressed in psoriatic lesional skin. However, cellular and molecular mechanism by which IL-17A exerts its function on keratinocyte is incompletely understood. To understand IL-17A mediated signal transduction pathways, gene expression profiling was done and differentially expressed genes were analysed by IPA software. Here, we demonstrate that during IL-17A signaling total cholesterol levels were elevated, which in turn resulted in the suppression of genes of cholesterol and fatty acid biosynthesis. We found that accumulation of cholesterol was essential for IL-17A signaling as reduced total cholesterol levels by methyl β cyclodextrin (MBCD), significantly decreased IL-17A induced secretion of CCL20, IL-8 and S100A7 from the keratinocytes. To our knowledge this study for the first time unveils that high level of intracellular cholesterol plays a crucial role in IL-17A signaling in keratinocytes and may explain the strong association between psoriasis and dyslipidemia.

Topics: Adolescent; Adult; Aged; beta-Cyclodextrins; Cell Differentiation; Cell Proliferation; Chemokine CCL20; Child; Cholesterol; Dyslipidemias; Fatty Acids; Female; Gene Expression Profiling; Gene Expression Regulation; Humans; Interleukin-17; Interleukin-8; Keratinocytes; Male; Middle Aged; Psoriasis; S100 Calcium Binding Protein A7; S100 Proteins; Signal Transduction

Neutrophil (PMN) leukocytes participate to the initial phases of atherosclerosis through the release of Interleukin 8 (CxCL8; IL-8) that contribute to amplification of inflammation. Aim of the study is to investigate the production of IL-8 by PMN leukocytes from dyslipidemic patients treated with simvastatin.. In 15 dyslipidemic subjects with moderately increased cardiovascular risk, assessed by Framingham Risk Score, blood samples were obtain to investigate PMNs IL-8 production [at baseline and after N-formyl-Met-Leu-Phe (fMLP) stimulation] before and after long-term (1-year) simvastatin treatment.. The resting release of IL-8 was higher in dyslipidemic patients at baseline when compared with control subjects (p < 0.05). One year of treatment was significantly associated with reduced IL-8 production (p < 0.01). Moreover, the fMLP-induced IL-8 production in dyslipidemic untreated patients was higher than that of controls (p < 0.05) and was reduced after simvastatin treatment (p < 0.01). IL-8 release after 1 year of treatment was reduced to levels which were lower than those observed in control subjects both for resting and stimulated cytokine production (p < 0.01).. Prolonged treatment with simvastatin is associated with a reduction of IL-8 production, suggesting the possibility of statin to modulate the pro-inflammatory response in PMNs of patients with moderately increased cardiovascular risk.

Topics: Adult; Aged; Anti-Inflammatory Agents; Biomarkers; Case-Control Studies; Down-Regulation; Dyslipidemias; Female; Humans; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Inflammation Mediators; Interleukin-8; Male; Middle Aged; Neutrophils; Simvastatin; Time Factors; Treatment Outcome

Many studies have indicated a role for cytokines in chronic kidney disease (CKD). The aim of this study was to evaluate plasma and urinary levels of monocyte chemoattractant protein-1 (MCP-1/CCL2), transforming growth factor-beta1 (TGF-β1), and interleukin-8 (IL-8/CXCL8) in pediatric patients with CKD stages 2-4.. Cytokines were measured in 37 healthy controls and in 42 CKD patients by enzyme-linked immunoassay. Patients were divided into groups according to CKD etiology: glomerular disease (group 1, n = 11) and congenital anomalies of the kidney and urinary tract (group 2, n = 31). Urinary cytokine measurements were standardized for creatinine.. Plasma and urinary levels of MCP-1/CCL2 were significantly higher in both CKD groups compared to the control group. Between the two CKD groups, only urinary MCP-1/CCL2 levels were significantly different, with MCP-1/CCL2 levels higher in group 1 patients. Plasma and urinary levels of IL-8/CXCL8 and TGF-β1 were undetectable in the control group but comparable between the two CKD groups. In group 1 patients, urinary MCP-1/CCL2 levels were negatively correlated to serum albumin levels and positively correlated to the levels of total cholesterol and triglycerides. In group 2 patients, urinary levels of IL-8/CXCL8 were negatively correlated with the estimated glomerular filtration rate and positively correlated with body mass index.. Differences in cytokine profiles may be related to CKD etiology and other disease-associated alterations.

Topics: Adolescent; Biomarkers; Case-Control Studies; Chemokine CCL2; Child; Cholesterol; Creatinine; Cross-Sectional Studies; Dyslipidemias; Enzyme-Linked Immunosorbent Assay; Female; Glomerulonephritis; Humans; Inflammation Mediators; Interleukin-8; Male; Renal Insufficiency, Chronic; Transforming Growth Factor beta1; Triglycerides; Urogenital Abnormalities; Vesico-Ureteral Reflux

Epoxyeicosatrienoic acids (EETs) have been shown to have antiinflammatory effects and therefore may play a role in preventing vascular inflammatory and atherosclerotic diseases. Soluble epoxide hydrolase (s-EH) converts EETs into less bioactive dihydroxyeicosatrienoic acids. Thus, inhibition of s-EH can prevent degradation of EETs and prolong their effects. The present study aimed to test the hypothesis that inhibition of s-EH has vascular protective effects.. Six-month-old apolipoprotein E-deficient mice were chronically infused with angiotensin II (1.44 mg/kg/d) for 4 weeks to induce abdominal aortic aneurysm (AAA), accelerate atherosclerosis development and carotid artery ligation-induced vascular remodeling. The mice were treated with a novel s-EH inhibitor, AR9276 (1.5 g/L in drinking water) or vehicle for 4 weeks. The results demonstrated that AR9276 significantly reduced the rate of AAA formation and atherosclerotic lesion area, but had no effect on ligation-induced carotid artery remodeling. These effects were associated with a reduction of serum lipid, IL-6, murine IL-8-KC, and IL-1alpha, and downregulation of gene expressions of ICAM-1, VCAM-1, and IL-6 in the arterial wall.. The present data demonstrate that treatment with an s-EH inhibitor attenuates AAA formation and atherosclerosis development. The attendant downregulation of inflammatory mediators and lipid lowering effects may both contribute to the observed vascular protective effects.

Topics: Administration, Oral; Angiotensin II; Animals; Aortic Aneurysm, Abdominal; Apolipoproteins E; Atherosclerosis; Biological Availability; Carotid Arteries; Cholesterol; Disease Models, Animal; Down-Regulation; Dyslipidemias; Enzyme Inhibitors; Epoxide Hydrolases; Inflammation Mediators; Intercellular Adhesion Molecule-1; Interleukin-1alpha; Interleukin-6; Interleukin-8; Ligation; Male; Mice; Mice, Knockout; Vascular Cell Adhesion Molecule-1

Endothelial lipotoxicity has been implicated in the pathogenesis of multiple stages of cardiovascular disease from early endothelial dysfunction to manifest atherosclerosis and its complications. Saturated free fatty acids are the major inducers of endothelial cell apoptosis and inflammatory cytokines. In humans, the enzyme human stearoyl-CoA desaturase-1 (hSCD-1) is the limiting step of the desaturation of saturated to monounsaturated fatty acids. Since we could demonstrate the expression of SCD-1 in primary human arterial endothelial cells (HAECs), we aimed to prove a beneficial role of upregulated hSCD-1 expression. In contrast to other cells that are less susceptible to lipotoxicity, hSCD-1 was not upregulated in HAECs upon palmitate treatment. Following that, we could show that upregulation of hSCD-1 using the LXR activator TO-901317 in HAECs protects the cells against palmitate-induced lipotoxicity, cell apoptosis, and expression of inflammatory cytokines IL-6 and IL-8. Increased hSCD-1 activity was determined as increased C16:1/16:0 ratio and enhanced triglyceride storage in palmitate treated cells. The beneficial effect was clearly attributed to enhanced hSCD-1 activity. Overexpression of hSCD-1 blocked palmitate-induced cytotoxicity, and knockdown of hSCD-1 using siRNA abolished the protective effect of TO-901317 in HEK-293 cells. Additionally, inhibition of hSCD-1 with 10/12 CLA blocked the effect of TO-901317 on palmitate-induced lipotoxicity, cell apoptosis, and inflammatory cytokine induction in HAECs. We conclude that upregulation of hSCD-1 leads to a desaturation of saturated fatty acids and facilitates their esterification and storage, thereby preventing downstream effects of lipotoxicity in HAECs. These findings add a novel aspect to the atheroprotective actions of LXR activators in cardiovascular disease.

Topics: Blotting, Western; Cell Survival; DNA-Binding Proteins; Dyslipidemias; Endothelial Cells; Enzyme Induction; Fatty Acids, Nonesterified; Humans; Hydrocarbons, Fluorinated; Interleukin-6; Interleukin-8; Liver X Receptors; Orphan Nuclear Receptors; Palmitates; Receptors, Cytoplasmic and Nuclear; Reverse Transcriptase Polymerase Chain Reaction; RNA, Messenger; RNA, Small Interfering; Stearoyl-CoA Desaturase; Sulfonamides; Transfection; Up-Regulation

Topics: Adult; Anti-Inflammatory Agents; C-Reactive Protein; Diabetes Mellitus; Dyslipidemias; Humans; Interleukin-6; Interleukin-8; Klinefelter Syndrome; Male; Pioglitazone; Stroke; Thiazolidinediones; Tumor Necrosis Factor-alpha