Over the past decade, chronic inflammation in visceral adipose tissue (VAT) has gained acceptance as a lead promoter of insulin resistance in obesity. A great deal of evidence has pointed to the role of adipokines and innate immune cells, in particular, adipose tissue macrophages, in the regulation of fat inflammation ...

Chronic low-grade inflammation has emerged as a key contributor to the pathogenesis of Polycystic Ovary Syndrome (PCOS). A dietary trigger such as glucose is capable of inciting oxidative stress and an inflammatory response from mononuclear cells (MNC) of women with PCOS, and this phenomenon is independent of obesity. This is ...

We have investigated the gastroprotective effect of SEGA (3a), a newly synthesized tryptamine-gallic acid hybrid molecule against non-steroidal anti-inflammatory drug (NSAID)-induced gastropathy with mechanistic details. SEGA (3a) prevents indomethacin (NSAID)-induced mitochondrial oxidative stress (MOS) and dysfunctions in gastric mucosal cells, which play a pathogenic role in inducing gastropathy. SEGA (3a) ...

OBJECTIVE: Adipose tissue inflammation with immune cell recruitment plays a key role in obesity-induced insulin resistance (IR). Long-chain (LC) n-3 polyunsaturated fatty acids (PUFA) eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) have anti-inflammatory potential; however, their individual effects on adipose IR are ill defined. We hypothesized that EPA and DHA ...

The aim of this study was to investigate the role of insulin receptor substrate-2 (IRS-2) mediated signal in macrophages on the accumulation of macrophages in the vascular wall. Mice transplanted with IRS-2(-/-) bone marrow, a model of myeloid cell restricted defect of IRS-2, showed accumulation of monocyte chemoattractant protein-1-expressing macrophages ...

Toll-like receptors are pattern-recognition receptors of the innate immune system that are activated during viral, bacterial or other infections, as well as during disease progression of type 1 and type 2 diabetes. Toll-like receptor 5 (TLR-5) specifically recognizes bacterial infection through binding of flagellin from pathogenic bacteria such as Salmonella ...

Equine metabolic syndrome (EMS) is a condition of obese horses characterized by insulin resistance, systemic inflammation, and an increased risk of laminitis. The pathogenesis of EMS is thought, in part, to be due to inflammatory proteins produced by adipose tissue. Reducing inflammation may decrease the incidence of laminitis in horses ...

Background/Aims: CJ-20001 is a phytopharmaceutical agent and currently being investigated in a Phase II trial for the treatment of acute and chronic gastritis patients in Korea. In this study we addressed the protective effects of CJ-20001 against water immersion restraint stress (WIRS)-induced gastric injury in rats and studied the underlying ...

Inflammation plays a key role in the pathogenesis of obesity. Chronic overfeeding leads to macrophage infiltration in the adipose tissue, resulting in proinflammatory cytokine production. Both microbial and endogenous danger signals trigger assembly of the intracellular innate immune sensor Nlrp3, resulting in caspase-1 activation and production of proinflammatory cytokines IL-1β ...

The aim of the present study was to determine whether timing of insulin administration influences the hepatic and serum proinflammatory and anti-inflammatory cytokines during endotoxemia stimulated by lipopolysaccharide (LPS). Eighty-one male Sprague-Dawley rats were divided into different time groups and insulin was given 30 min pre-LPS administration or hour 0, 1, 3, ...

In this work our aim was to determine whether L arginine (a known insulinotropic amino acid) can promote a shift of β-cell intermediary metabolism favoring glutathione (GSH+GSSG) anti-oxidant responses, stimulus-secretion coupling, and functional integrity. Clonal BRIN-BD11 β cells and mouse islets were cultured for 24h at various L-arginine concentrations (0 ...

Abstract Various pancreatic β-cell stressors, including cytokines, are known to induce oxidative stress, resulting in apoptotic/necrotic cell death and inhibition of insulin secretion. Traditionally, olive leaves or fruits are used for treating diabetes, but the cellular mechanism(s) of their effects are not known. We examined the effects of Olea europea ...

Reactive oxygen species (ROS) are important mediators to induce pancreatitis. Serum levels of antioxidant enzymes and carotenoids including lycopene are lower in patients with pancreatitis than those of healthy subjects. The cholecystokinin (CCK) analog cerulein induces similar pathologic events as shown in human pancreatitis. Recent studies show that high doses ...

Cholecystokinin octapeptide (CCK-8) is a typical brain-gut peptide that exerts a variety of physiological actions in both the peripheral and central nervous systems. Our laboratory has previously reported that CCK-8 produces immunoregulatory action through activating CCK receptor (CCK1R/CCK2R) expression on immune cell surfaces. In the present study, we investigated the ...

TLR3, one of the TLRs involved in the recognition of infectious pathogens for innate and adaptive immunity, primarily recognizes viral-associated dsRNA. Recognition of dsRNA byproducts released from apoptotic and necrotic cells is a recently proposed mechanism for the amplification of toxicity, suggesting a pivotal participation of TLR3 in viral infection, ...

OBJECTIVE Macrophage secretion of proinflammatory cytokines contributes to the pathogenesis of obesity-related insulin resistance. An important regulator of inflammation is the suppressor of cytokine signaling-1 (SOCS1), which inhibits the JAK-STAT and toll-like receptor-4 (TLR4) pathways. Despite the reported role of SOCS1 in inhibiting insulin signaling, it is surprising that a ...

Atherosclerosis is rapidly gaining recognition as an inflammatory disease showing contribution from innate and adaptive immunity pathways towards disease initiation and progression. Components of adaptive immunity especially T cells, are shown to be involved in atherogenesis and subsets of T cells are known to drive/ dampen inflammatory processes in atherosclerosis. ...

Almost half the world's population is infected by Helicobacter pylori (H. pylori). This bacterium increases the production of reactive oxygen species (ROS) and reactive nitrogen species (RNS) in human stomach, and this has been reported to impact upon gastric inflammation and carcinogenesis. However, the precise mechanism by which H. pylori ...

Imatinib Mesylate (Gleevec) is a drug that potently counteracts diabetes both in humans and in animal models for human diabetes. We have previously reported that this compound in human pancreatic islets stimulates NF-κB signaling and islet cell survival. The aim of this study was to investigate control of NF-κB post-translational ...

Current research depicts specific modes of immunity and energy metabolism as being interrelated at the molecular, cellular, organ and organism level. Hence, whereas M2 (alternatively-activated) macrophages dominate insulin-sensitive adipose tissue in the lean, M1-skewed (classically-activated) macrophages accumulate in parallel to adiposity in the obese, and promote inflammation and insulin resistance, ...

Macrophage foam cell is the predominant cell type in atherosclerotic lesions. Removal of excess cholesterol from macrophages thus offers effective protection against atherosclerosis. Here we report that a protein kinase A (PKA)-anchoring inhibitor, st-Ht31, induces robust cholesterol/phospholipid efflux, and ATP-binding cassette transporter A1 (ABCA1) greatly facilitates this process. Remarkably, we ...

High-mobility group box protein 1 (HMGB1) is a DNA-binding protein and cytokine highly expressed in atherosclerotic lesions, but its pathophysiological role in atherosclerosis is unknown. We investigated its role in the development of atherosclerosis in ApoE-/- mice. Apolipoprotein E-deficient (ApoE-/-) mice fed a high-fat diet were administered a monoclonal anti-HMGB1 ...

The importance of the involvement of the immune system in the development and progression of atherosclerosis was first suggested after the discovery of T cells in atherosclerotic lesions in 1990s. In order to be activated, T cell needs to be presented with an antigen but how this occurs in atherosclerosis ...

The atherosclerotic process is accelerated in patients with systemic lupus erythematosus (SLE). In addition to a robust lipid-lowering effect, various immunomodulatory functions have been ascribed to statins. By virtue of the latter they may be able to reduce atherosclerotic vascular disease in SLE by inhibiting immune activation within the arterial ...

Abstract Accumulating evidence suggests that inflammatory pathways play an essential role in all stages of atherogenesis. Inflammatory processes are not only involved in plaque progression, but seem also to play a critical role in plaque rupture. Members of the tumor necrosis factor (TNF) superfamiliy are potent regulators of inflammation and ...

The vascular cell apoptosis may play an important role in the development of atherosclerosis. Reticulons, the only molecular so far to participate in all three apoptosis signaling pathways, may be a novel player in the progress of AS. We presumes that reticulons may belong to the principle node of apoptosis ...

Statins lower cholesterol by inhibiting 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase, the rate-limiting enzyme in the biosynthesis of cholesterol. However, severe adverse events, including myalgias and rhabdomyolysis, have been reported with statin treatment. Different mechanisms have been proposed to explain statin-induced myopathy, including reduction of mevalonate pathway products, induction of apoptosis, ...

San-Huang-Xie-Xin-Tang (SHXXT) is a traditional Chinese medicine and it has been shown to have an anti-inflammatory effect. Since inflammation is one of the major mechanisms of atherosclerosis, we aimed to investigate anti-atherosclerotic effect of SHXXT in human aortic smooth muscle cells (HASMCs). Human aortic smooth muscle cells (HASMCs) were used ...

To test whether severe ascorbic acid deficiency in macrophages affects progression of early atherosclerosis, we used fetal liver cell transplantation to generate atherosclerosis-prone apolipoprotein E-deficient (apoE(-/-)) mice that selectively lacked the ascorbate transporter (SVCT2) in hematopoietic cells, including macrophages. After 13 weeks of chow diet, apoE(-/-) mice lacking the SVCT2 ...

Carotid plaques remodel toward a more stable phenotype after stroke, but not after TIA. Connective tissue growth factor (CTGF) is involved in extracellular matrix production and is expressed in atherosclerotic plaques. We studied the role of CTGF in plaque remodeling after stroke and TIA. Atherosclerotic plaques from carotid endarterectomy of ...

Inflammation and activation of immune cells are key mechanisms in the development of atherosclerosis. Previous data indicate important roles for monocytes and T lymphocytes in lesion formation, whereas the contribution of neutrophils remains to be firmly established. Here, we investigate the effect of hypercholesterolemia on peripheral neutrophil counts, neutrophil recruitment ...

It has been reported that HMG-CoA reductase inhibitors such as atorvastatin induce vascular smooth muscle cell (SMC) apoptosis in vitro. However, this effect remains to be demonstrated in vivo. The present studies were designed to test the ability of atorvastatin to induce SMC apoptosis in vivo, using the spontaneously hypertensive ...

Hydrolysis of intracellular cholesterol ester (CE) is the key step in the reverse cholesterol transport in macrophage foam cells. We have recently shown that neutral cholesterol ester hydrolase (Nceh)1 and hormone-sensitive lipase (Lipe) are key regulators of this process in mouse macrophages. However, it remains unknown which enzyme is critical ...

Sphingomyelin deposition and metabolism occurs in the atherosclerotic plaque, leading to the formation of sphingosine-1-phosphate (S1P), which activates G protein-coupled receptors to regulate vascular and immune cells. The role of S1P receptors in atherosclerosis has not been examined. We tested the hypothesis that S1P receptor-2 (S1PR2) regulates atherosclerosis. Apoe(-/-) S1pr2(-/-) ...

CD36 is a scavenger receptor known to play a critical role in the development of atherosclerosis by mediating the uptake of oxidized low-density lipoproteins (oxLDL) by macrophages, thus leading to foam cell formation. It is now generally recognized that the immune system has a pivotal role in the pathogenesis of ...

The skeletal muscles are the major living component of the human body. They are constituted by stable cells, the myofibres, and by adult multipotent stem cells, the satellite cells, which can multiply to regenerate and repair the damaged tissues. Injections of DNA in muscle cells have been used to produce ...

Chronic and intermittent ischemic vascular disorders represent a burgeoning clinical challenge. Previous studies have focused on the idea that therapeutic angiogenesis strategies could alleviate tissue ischemia; however, it is now appreciated that vascular disease is not simply limited to vascular wall cells but also influenced by simultaneously occurring inflammatory responses. ...

Currently, many stroke-prone individuals take antithrombotic drugs, which have known antiplatelet properties, to decrease stroke incidence. There is now evidence that this regimen could also reduce stroke severity through neuroprotective, nonplatelet mechanisms that include anti-inflammatory processes. Inflammation was found to play an important role in atherosclerosis/thrombosis development and acute stroke ...

To summarize the current knowledge on the origin and physiological function of T helper 17 (Th17) and discuss the contrasting results pertaining to the role of Th17 and interleukin-17 (IL-17) in atherosclerosis. Atherosclerosis is a chronic inflammatory arterial disease driven by both innate and adaptive immune responses to modified lipoproteins. ...

Immune modulation of neointimal formation after vascular injury has been investigated for several decades but the complexities involved continue to obscure a clearer understanding of the process. The rapidly changing field of immunology makes this knowledge imperative. The review discusses immune factors involved in the response to vascular injury. Although ...

Statins are one of the most important medications in cardio-vascular diseases since they block cholesterol synthesis by inhibiting the 3-hydroxy-3-methylglutaryl coenzyme A reductase and thus reduce low density lipoprotein concentrations. In the last years, numerous pleiotropic properties of statins have been described, beyond their well-known lipid lowering function. In particular, ...

Inflammatory disorders are characterized by the influx of immune cells into the vascular wall of veins and/or arteries in response to stimuli such as oxidized-LDL and various pathogens. These factors stimulate the local production of pro-inflammatory cytokines by macrophages and other cells that promote various inflammatory diseases such as atherosclerosis, ...

The role of inflammation in all stages of atherosclerosis has been actively investigated, with an emphasis on the discovery of novel and innovative drugs for treatment and prevention. The anti-inflammatory and immunomodulatory capacity of cannabinoids are well established, and these agents have a broad therapeutic potential in various inflammatory diseases, ...

The synthesis and utility of a multimodal theranostic nanoagent based upon magnetofluorescent nanoparticles for the treatment of inflammatory atherosclerosis is described. These particles are modified with near-infrared fluorophores and light-activated therapeutic moieties, which allow for the optical determination of agent localization and phototoxic activation at spectrally distinct wavelengths. The resulting ...

The hedgehog signal pathway plays a crucial role in the angiogenesis and vascular remodeling. However, the function of this pathway in the pulmonary vascular smooth cell proliferation in response to hypoxia remains unknown. In this study, we have demonstrated that the main components of the hedgehog pathway, including sonic hedgehog ...

Macrophages play central roles in immunity and homeostasis, and contribute to the pathogenesis of atherosclerosis through their accumulation of cholesterol and the production of inflammatory mediators and cytokines. Recent studies indicate that oxysterols influence diverse aspects of macrophage biology. Rather than simply being intermediates of cholesterol catabolism, oxysterols are also ...

Considerable evidence shows atherosclerosis to be a chronic inflammatory disease in which immunity to self-antigens contributes to disease progression. We recently identified the collagen type V [col(V)] α1(V) chain as a key autoantigen driving the Th17-dependent cellular immunity underlying another chronic inflammatory disease, obliterative bronchiolitis. Because specific induction of α1(V) ...

Endothelial cell apoptosis is a pivotal step in the development of atherosclerotic disease. Regeneration of the damaged endothelium is an attractive therapy option in the prevention and treatment of atherosclerotic disease. Apoptosis is associated with the release of microparticles (MP). Besides their role as marker of cell damage, recent reports ...

Rationale Monocytes entering tissues, including advanced atherosclerotic plaques, rapidly mature and adapt to their new microenvironment. Intraplaque haemorrhage promotes human atherosclerosis progression and destabilisation via a dual metabolic challenge: cholesterol-enriched erythrocyte membranes and haem-iron. In human coronary culprit lesions, we recently described a novel macrophage subset (M-haem) with atheroprotective properties ...

Rationale Macrophages in atherosclerotic plaques are a heterogeneous population. To uncover signatures of classical (M1) or alternative (M2) macrophage polarisation during plaque instability, we compared cytokine and chemokine production via Luminex profiling in asymptomatic human carotid plaques with carotid plaques in the territory of recent focal neurological symptomatology. Methodology Carotid ...