interleukin-8 and Arrhythmias--Cardiac

Adiponectin (ADIPO) and interleukin-8 (IL-8) are proteins that play a significant, albeit opposing, role in metabolic syndrome (MetS). The reported data on the effect of physical activity on the levels of these hormones in the population of people with MetS are conflicting. The aim of the study was to evaluate the changes in hormone concentrations, insulin-resistance indices and body composition after two types of training. The study included 62 men with MetS (age 36.6 ± 6.9 years, body fat [BF] = 37.53 ± 4.5%), randomly assigned to: an experimental group EG1 (n = 21) with aerobic exercise intervention, an experimental group EG2 (n = 21) with combined aerobic and resistance exercise intervention, both for 12 weeks, and a control group CG (n = 20) without interventions. Anthropometric measurements and body composition (fat-free mass [FFM], gynoid body fat [GYNOID]), as well as a biochemical blood analysis (adiponectin [ADIPO], interleukin-8 [IL-8], homeostatic model assessment-adiponectin (HOMA-AD) and homeostatic model assessment-triglycerides (HOMA-TG) were performed at baseline, and at 6 and 12 weeks of intervention and 4 weeks after the intervention (follow-up). Intergroup (between groups) and intragroup (within each group) changes were statistically evaluated. In the experimental groups EG1 and EG2, no significant changes were observed in the ADIPO concentration, but a decrease of GYNOID and insulin-resistance indices was confirmed. The aerobic training led to favorable changes in IL-8 concentration. The use of combined resistance and aerobic training led to improved body composition, decreased waist circumference and better insulin-resistance indices in men with MetS.

Topics: Adiponectin; Adult; Arrhythmias, Cardiac; Body Mass Index; Carbohydrate Metabolism; Humans; Insulin; Insulin Resistance; Interleukin-8; Male; Metabolic Syndrome; Obesity

Atrial arrhythmias are associated with an increased risk of stroke and death in the elderly. The risk and predictive factors of recurrent atrial arrhythmias in elderly patients after coronary stenting are not well known.. This research sought to investigate the roles of pro- and anti-inflammatory cytokine imbalances in different types of recurrent atrial arrhythmias in elderly patients defined as individuals aged 65 years or older after sirolimus eluting stent (Cordis, Warren, New Jersey) implantation.. We measured interleukin-1β (IL-1β), interleukin-6 (IL-6), interleukin-8 (IL-8), tumor necrosis factor-α (TNF-α), interleukin-10 (IL-10), interleukin-17 (IL-17), interleukin-13 (IL-13) and interleukin- 37 (IL-37) in elderly patients with recurrent atrial arrhythmias and assessed the impact of pro- and antiinflammatory cytokine imbalances on recurrent atrial arrhythmias in elderly patients after coronary stenting.. Levels of IL-1 β, IL-6, IL-8, and TNF-α were remarkably increased (p<0.001), and IL-10, IL- 17, IL-13, and IL-37 were remarkably lowered (p<0.001) in elderly patients with recurrent atrial arrhythmias after coronary stent implantation. Imbalance of pro- and anti-inflammatory cytokines induced recurrent atrial arrhythmias after coronary stenting. Pro- and anti-inflammatory cytokine imbalances may be used to identify elderly patients who have an increased risk of developing recurrent atrial arrhythmias after coronary stenting.. The imbalance of pro- and anti-inflammatory cytokines was associated with recurrent atrial arrhythmias in elderly patients after coronary stenting. Pro- and anti-inflammatory cytokines may be clinically useful biomarkers for predicting recurrent atrial arrhythmias in elderly patients after coronary stent implantation.

Topics: Aged; Anti-Inflammatory Agents; Arrhythmias, Cardiac; Cytokines; Drug-Eluting Stents; Humans; Interleukin-10; Interleukin-13; Interleukin-6; Interleukin-8; Tumor Necrosis Factor-alpha

In the member countries of the Organization for Economic Co-operation and Development (OECD), overweight and obesity affect the majority of the population. The use of environmental chemicals, such as the plasticizer DEHP, has largely increased simultaneously with this development. DEHP is an "obesogen" that interferes with normal adipocyte differentiation and energy homeostasis. Obesity in turn is accompanied by chronic low-grade adipose tissue inflammation, leading to metabolic disorders such as type II diabetes. The main actors in adipose tissue inflammation are adipocytes and macrophages. However, the impact of DEHP on adipose tissue inflammation and the crosstalk between adipocytes and macrophages are unknown and the subjects of the current study. The influence of DEHP on inflammation was investigated in human Simpson-Golabi-Behmel syndrome (SGBS)-derived adipocytes and human THP-1 macrophages. The proinflammatory markers IL8, MCP1, IL1β, TNFα and others were measured (qRT-PCR, ELISA) in SGBS-derived adipocytes treated with DEHP [day 0 (d0)-d4; 50 µg/ml] and THP-1 macrophages cultured with conditioned medium (CM) from DEHP-treated adipocytes (SGBS-CM) (from d4 and d8). DEHP exposure led to a proinflammatory state in SGBS-derived adipocytes (e.g., increased secretion of IL8 and MCP1). Surprisingly, exposure of THP-1 macrophages to SGBS-CM did not show DEHP-induced effects. However, we demonstrated that medium containing (pre)adipocyte-secreted factors had a significant impact on the expression and secretion of macrophage and inflammatory markers in THP-1 macrophages in general and led to the significantly increased accumulation of intracellular lipid droplets.

Topics: Adipocytes; Arrhythmias, Cardiac; Chemokine CCL2; Culture Media, Conditioned; Cytokines; Diethylhexyl Phthalate; Fluorescence; Gene Expression Regulation; Genetic Diseases, X-Linked; Gigantism; Heart Defects, Congenital; Humans; Inflammation; Intellectual Disability; Interleukin-8; Lipid Droplets; Macrophages; RNA, Messenger; THP-1 Cells

Adipocyte-macrophage crosstalk plays a critical role to regulate adipose tissue microenvironment and cause chronic inflammation in the pathogenesis of obesity. Interleukin-29 (IL-29), a member of type 3 interferon family, plays a role in host defenses against microbes, however, little is known about its role in metabolic disorders. We explored the function of IL-29 in the pathogenesis of obesity-induced inflammation and insulin resistance. We found that serum IL-29 level was significantly higher in obese patients. IL-29 upregulated IL-1β, IL-8, and monocyte chemoattractant protein-1 (MCP-1) expression and decreased glucose uptake and insulin sensitivity in human Simpson-Golabi-Behmel syndrome (SGBS) adipocytes through reducing glucose transporter 4 (GLUT4) and AKT signals. In addition, IL-29 promoted monocyte/macrophage migration. Inhibition of IL-29 could reduce inflammatory cytokine production in macrophage-adipocyte coculture system, which mimic an obese microenvironment. In vivo, IL-29 reduced insulin sensitivity and increased the number of peritoneal macrophages in high-fat diet (HFD)-induced obese mice. IL-29 increased M1/M2 macrophage ratio and enhanced MCP-1 expression in adipose tissues of HFD mice. Therefore, we have identified a critical role of IL-29 in obesity-induced inflammation and insulin resistance, and we conclude that IL-29 may be a novel candidate target for treating obesity and insulin resistance in patients with metabolic disorders.

Topics: Adipocytes; Adipose Tissue; Animals; Arrhythmias, Cardiac; Cell Differentiation; Cell Movement; Chemokine CCL2; Diet, High-Fat; Genetic Diseases, X-Linked; Gigantism; Glucose Transporter Type 4; Heart Defects, Congenital; Inflammation; Insulin Resistance; Intellectual Disability; Interferons; Interleukin-1beta; Interleukin-6; Interleukin-8; Interleukins; Lipopolysaccharides; Macrophages; Mice, Inbred C57BL; Mice, Obese; Obesity; Phosphorylation; Proto-Oncogene Proteins c-akt; Receptors, Interleukin; Up-Regulation

High serum concentrations of TNF-related apoptosis-inducing ligand (TRAIL), a member of the tumor necrosis factor protein family, are found in patients with increased BMI and serum lipid levels. In a model of murine obesity, both the expression of TRAIL and its receptor (TRAIL-R) is elevated in adipose tissue. Accordingly, TRAIL has been proposed as an important mediator of adipose tissue inflammation and obesity-associated diseases. The aim of this study was to investigate if TRAIL regulates inflammatory processes at the level of the adipocyte. Using human Simpson-Golabi-Behmel syndrome (SGBS) cells as a model system, we found that TRAIL induces an inflammatory response in both preadipocytes and adipocytes. It stimulates the expression of interleukin 6 (IL-6), interleukin 8 (IL-8) as well as the chemokines monocyte chemoattractant protein-1 (MCP-1) and chemokine C-C motif ligand 20 (CCL-20) in a time- and dose-dependent manner. By using small molecule inhibitors, we found that both the NFκB and the ERK1/2 pathway are crucial for mediating the effect of TRAIL. Taken together, we identified a novel pro-inflammatory function of TRAIL in human adipocytes. Our findings suggest that targeting the TRAIL/TRAIL-R system might be a useful strategy to tackle obesity-associated adipose tissue inflammation.

Topics: Adipocytes; Adult; Arrhythmias, Cardiac; Cells, Cultured; Chemokine CCL2; Chemokine CCL20; Genetic Diseases, X-Linked; Gigantism; Heart Defects, Congenital; Humans; Inflammation; Intellectual Disability; Interleukin-6; Interleukin-8; Mitogen-Activated Protein Kinases; NF-kappa B; Signal Transduction; TNF-Related Apoptosis-Inducing Ligand

An altered IL-18 pathway in patients with coronary artery disease has recently been described and this cytokine was shown to be of clinical and prognostic utility. Cardiomyocytes are a target of this cytokine which exerts inflammatory, hypertrophic and profibrotic activities.. The aim of the study was to verify the ability of IL-18 to induce expression of other pro/anti-inflammatory cytokines and to analyse the relationship between these molecules in serum from patients with heart rhythm disorders and coronary artery disease.. All patients in the study were divided into two groups: with heart rhythm disorders and without but with diagnosed coronary artery disease. Heart rhythm disorders included sinus node dysfunction, bradycardia and tachycardia.. The interrelationships among all tested clinical, biochemical and inflammatory parameters with a dependence on median IL-18 values were checked. From all tested parameters only cytokines IL-8, IL-10 and VEGF, were associated with the serum IL-18 levels.. IL-18, IL-8 and VEGF were identified as a factors involved in heart rhythm disorders and coronary artery disease patho-physiology and regarded as markers of prognostic significance and potential therapeutic targets. The demonstration of their in vivo relationship added new insights into the understanding of the interdependence of inflammatory pathways in patients with heart rhythm disorders or coronary artery disease.

Topics: Aged; Aged, 80 and over; Arrhythmias, Cardiac; Biomarkers; Coronary Artery Disease; Cross-Sectional Studies; Female; Humans; Interleukin-10; Interleukin-18; Interleukin-8; Male; Middle Aged; Vascular Endothelial Growth Factor A

The obesity-associated inflammation of white adipose tissue (WAT) is one of the factors leading to the development of related diseases such as insulin resistance and liver steatosis. Recently, microRNAs (miRNAs) were identified as important regulators of WAT functions. Herein, we cultured human Simpson-Golabi-Behmel syndrome (SGBS) adipocytes with macrophage-conditioned medium (MacCM) and performed an Affimetrix miRNA array to identify miRNAs differentially expressed under inflammatory conditions. We identified 24 miRNAs differentially expressed upon inflammation in human adipocytes and miR-146a was the most up-regulated miRNA species. In subcutaneous WAT, miR-146a was elevated in both human and murine obesity. Transfection of miR-146a mimics prevented the MacCM-induced inflammatory response in SGBS adipocytes as seen by reduced levels of IL-8 and MCP-1 mRNA and protein. We identified IRAK1 and TRAF6 as targets of miR-146a in human adipocytes and detected a reduced inflammation-induced activation of JNK and p38 upon miR-146a transfection. Taken together, we could show that miR-146a reduces the inflammatory response in human adipocytes. In a negative feedback loop miR-146a might contribute to the regulation of inflammatory processes in WAT and possibly prevent an overwhelming inflammatory response.

Topics: Adipocytes, White; Adipose Tissue, White; Arrhythmias, Cardiac; Chemokine CCL2; Culture Media, Conditioned; Feedback, Physiological; Female; Gene Expression Regulation; Genetic Diseases, X-Linked; Gigantism; Heart Defects, Congenital; Humans; Inflammation; Intellectual Disability; Interleukin-1 Receptor-Associated Kinases; Interleukin-8; Intracellular Signaling Peptides and Proteins; Macrophages; MAP Kinase Kinase 4; MicroRNAs; Molecular Mimicry; Oligonucleotide Array Sequence Analysis; Oligoribonucleotides; p38 Mitogen-Activated Protein Kinases; Primary Cell Culture; RNA, Small Interfering; Signal Transduction; TNF Receptor-Associated Factor 6; Transfection

Immunoreactive signal for the desmosomal protein plakoglobin (γ-catenin) is reduced at cardiac intercalated disks in patients with arrhythmogenic right ventricular cardiomyopathy (ARVC), a highly arrhythmogenic condition caused by mutations in genes encoding desmosomal proteins. Previously, we observed a false-positive case in which plakoglobin signal was reduced in a patient initially believed to have ARVC but who actually had cardiac sarcoidosis. Sarcoidosis can masquerade clinically as ARVC but has not been previously associated with altered desmosomal proteins.. We observed marked reduction in immunoreactive signal for plakoglobin at cardiac myocyte junctions in patients with sarcoidosis and giant cell myocarditis, both highly arrhythmogenic forms of myocarditis associated with granulomatous inflammation. In contrast, plakoglobin signal was not depressed in lymphocytic (nongranulomatous) myocarditis. To determine whether cytokines might promote dislocation of plakoglobin from desmosomes, we incubated cultures of neonatal rat ventricular myocytes with selected inflammatory mediators. Brief exposure to low concentrations of interleukin (IL)-17, tumor necrosis factor-α (TNF-α), and IL-6 (cytokines implicated in granulomatous myocarditis) caused translocation of plakoglobin from cell-cell junctions to intracellular sites, whereas other potent cytokines implicated in nongranulomatous myocarditis had no effect, even at much higher concentrations. We also observed myocardial expression of IL-17 and TNF-α and elevated levels of serum inflammatory mediators, including IL-6R, IL-8, monocyte chemoattractant protein 1, and macrophage inflammatory protein 1β, in patients with ARVC (all P<0.0001 compared with controls).. The results suggest novel disease mechanisms involving desmosomal proteins in granulomatous myocarditis and implicate cytokines, perhaps derived in part from the myocardium, in disruption of desmosomal proteins and arrhythmogenesis in ARVC.

Topics: Adolescent; Adult; Aged; Animals; Arrhythmias, Cardiac; Autopsy; Biopsy; Cardiomyopathies; Case-Control Studies; Cells, Cultured; Chemokine CCL2; Chemokine CCL4; Child; Desmosomes; Female; gamma Catenin; Humans; Intercellular Junctions; Interleukin-17; Interleukin-6; Interleukin-8; Male; Middle Aged; Models, Animal; Myocarditis; Myocytes, Cardiac; Rats; Rats, Wistar; Sarcoidosis; Signal Transduction; Tumor Necrosis Factor-alpha; Ventricular Dysfunction, Right; Young Adult