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Anti-Inflammatory Activity of Quantum Energy Living Body on Lipopolysaccharide-Induced Murine RAW 264.7 Macrophage Cell Line
Abstract
Recent developments from science and medical science show a growing interest in the anti-inflammatory activity of natural materials. Inflammation is the body’s physiologic response to injurious stimulation and is known to be mediated by various pro-inflammatory cytokines (e.g. TNF-α, IL-1β, IL-6 etc) and iNOS (inducible nitric oxide synthase). Quantum energy living body (QELBY) powder is a fusion of a special ceramic powder with natural clay mineral classified as quantum energy radiating material (QERM). The powder, composed mostly of silicon dioxide, is known to radiate reductive radiant energy. This study was designed to evaluate the anti-inflammatory activities of QELBY powder on RAW 264.7 mouse macrophage cells. QELBY powder was mixed with DMEM media and was allowed to stand for 48 hours. Afterwards, the supernatant was taken and diluted to various concentrations (0,5,10,20,40 μg/ml) prior to use. CCK-8 assay was done to determine the effects on cell viability. In addition, NO assay performed to elucidate the effect of QELBY on the NO production of LPS-stimulated macrophages. Lastly, RT-PCR and Western blot analysis for the detection of the mRNA and protein expressions, respectively, of proinflammatory cytokines and iNOS was made. Results demonstrated that QELBY powder causes both an increase in cell proliferation and a concentration-dependent decrease in NO production. Moreover, the mRNA and protein expressions of pro-inflammatory cytokines and iNOS were also inhibited. Taken together, these show that QELBY powder has anti-inflammatory activity and could therefore be used further in the development of materials that induce such kinds of benefits.
... Details and composition are presented in a Korean patent (KP 10-1172018) [1] and published elsewhere [2]. This hydrophilic material shows variety of interesting properties, mostly related to the enhancement of various cell-biological processes [3,4]. Because of the diversity of enhancement effects, it is presumed that the mechanism is related to "something" present throughout the cell, the most likely substance being water. ...
... As a control we used natural silica powder, chosen because silica is the major component of QELBY. The study was also undertaken to complement earlier studies on cellular models of health and disease with promising results [3]. Since EZs were observed around QELBY particles, we explored whether the water that was in contact with QELBY, when separated centrifugally from the powder, could still influence early plant growth, specifically seed germination and early sapling formation. ...
A hydrophilic powder, QELBY, from the feldspar family of clay minerals was investigated for its ability to form structured or exclusion-zone (EZ) water. We demonstrated microsphere-free zones around different fractions of the QELBY powder or its hydrated pellet. Averaging approximately 100 μ m, these zones grew to a size similar to that formed in the vicinity of the Nafion standard. In the case of silica (control), only occasional microsphere-free zones of about 70 μ m were found. Further, studies to investigate QELBY’s energizing effect on germination and early sapling growth in brown chickpea seeds showed at least a 2-3-fold increase in root length and/or formation of shoots. This was seen in seeds bathed in QELBY supernatants or surrounded by QELBY powder outside the vials containing the seeds. This indirect effect was observed whether the QELBY was dry or hydrated.
Promotion of endogenous β-cell mass expansion could facilitate regeneration in patients with diabetes. We discovered that the secreted protein CTGF (aka CCN2) promotes adult β-cell replication and mass regeneration after injury via increasing β-cell immaturity and shortening the replicative refractory period. However, the mechanism of CTGF-mediated β-cell proliferation is unknown. Here we focused on whether CTGF alters cells of the immune system to enhance β-cell replication.
Using mouse models for 50% β-cell ablation and conditional, β-cell-specific CTGF induction, we assessed changes in immune cell populations by performing immunolabeling and gene expression analyses. We tested the requirement for macrophages in CTGF-mediated β-cell proliferation via clodronate-based macrophage depletion.
CTGF induction after 50% β-cell ablation increased both macrophages and T-cells in islets. An upregulation in the expression of several macrophage and T-cell chemoattractant genes was also observed in islets. Gene expression analyses suggest an increase in M1 and a decrease in M2 macrophage markers. Depletion of macrophages (without changes in T cell number) blocked CTGF-mediated β-cell proliferation and prevented the increase in β-cell immaturity.
Our data show that macrophages are critical for CTGF-mediated adult β-cell proliferation in the setting of partial β-cell ablation. This is the first study to link a specific β-cell proliferative factor with immune-mediated β-cell proliferation in a β-cell injury model.
Studies on monocyte and macrophage biology and differentiation have revealed the pleiotropic activities of these cells. Macrophages are tissue sentinels that maintain tissue integrity by eliminating/repairing damaged cells and matrices. In this M2-like mode, they can also promote tumor growth. Conversely, M1-like macrophages are key effector cells for the elimination of pathogens, virally infected, and cancer cells. Macrophage differentiation from monocytes occurs in the tissue in concomitance with the acquisition of a functional phenotype that depends on microenvironmental signals, thereby accounting for the many and apparently opposed macrophage functions. Many questions arise. When monocytes differentiate into macrophages in a tissue (concomitantly adopting a specific functional program, M1 or M2), do they all die during the inflammatory reaction, or do some of them survive? Do those that survive become quiescent tissue macrophages, able to react as naïve cells to a new challenge? Or, do monocyte-derived tissue macrophages conserve a “memory” of their past inflammatory activation? This review will address some of these important questions under the general framework of the role of monocytes and macrophages in the initiation, development, resolution, and chronicization of inflammation.
Regular exercise reduces the risk of chronic metabolic and cardiorespiratory diseases, in part because exercise exerts anti-inflammatory effects. However, these effects are also likely to be responsible for the suppressed immunity that makes elite athletes more susceptible to infections. The anti-inflammatory effects of regular exercise may be mediated via both a reduction in visceral fat mass (with a subsequent decreased release of adipokines) and the induction of an anti-inflammatory environment with each bout of exercise. In this Review, we focus on the known mechanisms by which exercise - both acute and chronic - exerts its anti-inflammatory effects, and we discuss the implications of these effects for the prevention and treatment of disease.
Great interest in herbal medicine as a potential source of phytopharmaceuticals has created the need to review common factors responsible for major diseases and body disorders. This review shows one such common factor in inflammation and the role herbal medicine can play. Traditional medicinal herbal remedies in the southern African region have long been used to treat various pain- or inflammation-related symptoms. Although the precise mechanisms of action of many herbal drugs have yet to be determined, some of them have been shown to exert anti-inflammatory and/or antioxidant effects in a variety of cells in the human and animal bodies. There is increasing evidence to indicate that both peripheral and central nervous system cells play a prominent role in the chronic inflammatory responses in the body system and anti-inflammatory herbal medicine and its constituents are being proved to be a potent protector against various pro-inflammatory mediators in diseases and disorders. These mediators have therefore been suspected of being the functional basis of diseases and disorders. The structural diversity of these medicinal herbs makes them a valuable source of novel lead compounds against the therapeutic molecular targets, cytokines and mediators, that have been newly discovered by the platforms of genomics, proteomics, metabolomics and high-throughput technologies. This article reviews the basic mechanisms of inflammation and the potential of 123 southern African plant species to be effective as chronic inflammatory disease preventive agents. With one third of these species there are no indications of the chemical composition, indicating possible subjects for further research.
Concanavalin A (Con A) causes severe TNF-α–mediated and IFN-γ–mediated liver injury in mice. In addition to their other functions, TNF-α and IFN-γ both induce the inducible nitric oxide (NO) synthase (iNOS). Using different models of liver injury, NO was found to either mediate or prevent liver damage. To further elucidate the relevance of NO for liver damage we investigated the role of iNOS-derived NO in the Con A model. We report that iNOS mRNA was induced in livers of Con A–treated mice within 2 hours, with iNOS protein becoming detectable in hepatocytes as well as in Kupffer cells within 4 hours. iNOS–/– mice were protected from liver damage after Con A treatment, as well as in another TNF-α–mediated model that is inducible by LPS in D-galactosamine–sensitized (GalN-sensitized) mice. iNOS-deficient mice were not protected after direct administration of recombinant TNF-α to GalN-treated mice. Accordingly, pretreatment of wild-type mice with a potent and specific inhibitor of iNOS significantly reduced transaminase release after Con A or GalN/LPS, but not after GalN/TNF-α treatment. Furthermore, the amount of plasma TNF-α and of intrahepatic TNF-α mRNA and protein was significantly reduced in iNOS–/– mice. Our results demonstrate that iNOS-derived NO regulates proinflammatory genes in vivo, thereby contributing to inflammatory liver injury in mice by stimulation of TNF-α production.
One of the primary physiological roles of nuclear factor-kappa B (NF-kappaB) is in the immune system. In particular, NF-kappaB family members control the transcription of cytokines and antimicrobial effectors as well as genes that regulate cellular differentiation, survival and proliferation, thereby regulating various aspects of innate and adaptive immune responses. In addition, NF-kappaB also contributes to the development and survival of the cells and tissues that carry out immune responses in mammals. This review, therefore, describes the role of the NF-kappaB pathway in the development and functioning of the immune system.
New ceramic composites from calcia-magnesia-silica system at a molar ratio of (CaO-MgO)/SiO2 closes to the unity and the addition of different amounts of zirconia (5 wt %, 15 wt % and 25 wt %) have been investigated. These systems powders were formed and fired at 1310 ± 20°C for 2 hr. Phase composition, microstructure, physical and mechanical properties of these composites were determined. The in-vitro bioactivities of these sintered composites were investigated by analysis of their ability for the formation of hydroxyapatite (HA) using SEM-EDS after their soaking in the simulated body fluid (SBF) for 7 days. The findings indicated that beginning of HA formation on the surface of all investigated composites. However, the composite containing 5 wt % ZrO2 gave clear tendency toward the formation-ability of HA typical to cauliflower morphology. The mechanical properties of the promised bioactive composite in term of Vickers hardness and fracture toughness were ~3 Gpa and ~2 Mpa. m1/2, respectively. The ceramic composite containing 5 wt % ZrO2 might be nominated to be implanted material because their property is quite similar to the properties of human cortical bone.
A close connection between inflammation and cancer has now been firmly established. While tumor initiation is typically independent of inflammatory events, immune cells infiltrating the tumor microenvironment secrete inflammatory cytokines that enhance the aberrant growth of tumor cells and thus facilitate tumor progression. Therefore, inflammation and tumor growth are usually interpreted as closely related on a systemic level but as distinct, independently regulated processes at a molecular level.
Recently, we reported that a sub-class of small GTPases, namely κB-Ras1 and κB-Ras2, regulate both inflammation and tumor growth, thereby providing a unique molecular bridge between the two biological processes.
Here, we briefly summarize the known contact points between inflammation and cancer, including oral cancers, and put into context the identification of κB-Ras proteins as molecular link between two independent pathways important for tumor growth.
Globally, respiratory infections cause more than 4 million deaths per year, with influenza and tuberculosis (TB) in particular being major causes of mortality and morbidity. Although immune cell activation is critical for killing respiratory pathogens, this response must be tightly regulated to effectively control and eliminate invading microorganisms while minimizing immunopathology and maintaining pulmonary function. The distinct microenvironment of the lung is constantly patrolled by alveolar macrophages (Mφ), which are essential for tissue homeostasis, early pathogen recognition, initiation of the local immune response, and resolution of inflammation. Here, we focus on recent advances that have provided insight into the relation between pulmonary Mφ, type I interferon (IFN) signaling, and the delicate balance between protective and pathological immune responses in the lung.
Copyright © 2015 Elsevier Ltd. All rights reserved.
Transplantation of bone-marrow derived mesenchymal stem cells (MSCs) has potential therapeutic effects on cardiac muscle repair. However, the underlying mechanism remains not completely clarified. Here we show that transplantation of MSCs significantly increased local recruitment of macrophages to facilitate cardiac muscle repair. MSCs-induced recovery of cardiac function and attenuation of fibrosis after injury were all abolished by either impaired macrophage infiltration, or by MSCs depletion after macrophage recruitment. However, angiogenesis seemed to be only affected by depletion of macrophages, but not by depletion of MSCs, suggesting that macrophages are responsible for the augmented angiogenesis after MSCs transplantation, while MSCs do not directly contribute to angiogenesis in the functional cardiac repair. Moreover, high level of transforming growth factor β 1 (TGFβ1) was detected in macrophages and high level of BMP7 was detected in MSCs, suggesting that MSCs not only may recruit macrophages to enhance angiogenesis to promote regeneration, but also may secrete BMP7 to contradict the fibrogenic effect of TGFβ1 by macrophages. Our study thus sheds new insight on the interaction of MSCs and macrophages in a functional cardiac repair triggered by MSCs transplantation.
Obesity is a state in which chronic low-grade inflammation persists in adipose tissues. Pro-inflammatory cytokines, including TNF-α, produced by adipose tissues have been implicated as active participants in the development of obesity-related diseases. Since TNF-α converting enzyme (TACE) is the major factor that induces soluble TNF-α, TACE has been noted as a pivotal regulator in this field. To reveal the role of TACE in adipose tissue inflammation, TACE-transgenic (TACE-Tg) and wild type (WT) mice were fed with high fat diet (HFD) or control diet for 16 weeks. At 13 weeks after the beginning of the diet, serum TNF-α and macrophage-related cytokine/chemokine levels were elevated in TACE-Tg mice fed with HFD (Tg-HFD mice), and the number of the so-called crown-like adipocyte was significantly increased in adipose tissues of Tg-HFD mice at the end of the experiment. Although macrophage infiltration was not detected in the adipose tissues at this time, fibrosis was observed around the crown-like adipocytes. These findings suggested that TACE overexpression induced macrophage infiltration and subsequent fibrosis in adipose tissues under HFD regimen. The collective evidence suggested that TACE could be a therapeutic target of HFD-induced obesity-related adipose tissue inflammation.
Sulforaphane, a naturally-occurring isothiocyanate present in cruciferous vegetables, has received wide attention for its potential to improve vascular function in vitro. However, its effect in vivo and the molecular mechanism of sulforaphane at physiological concentrations remain unclear. Here, we report that a sulforaphane concentration as low as 0.5 μM significantly inhibited TNF-α-induced adhesion of monocytes to human umbilical vein endothelial cells (HUVECs), a key event in the pathogenesis of atherosclerosis both in static and under flow conditions. Such physiological concentrations of sulforaphane also significantly suppressed TNF-α-induced production of monocyte chemotactic protein-1 (MCP-1), adhesion molecule sVCAM-1 and sE-Selectin, key mediators in the regulation of enhanced endothelial cell-monocyte interaction. Furthermore, sulforaphane inhibited TNF-α-induced NF-κB transcriptional activity, IκBα degradation and subsequent NF-κB p65 nuclear translocation in endothelial cells, suggesting that sulforaphane can inhibit inflammation by suppressing NF-κB signaling. In an animal study, sulforaphane (300 ppm) in a mouse diet significantly abolished TNF-α-increased ex vivo monocyte adhesion and circulating adhesion molecules and chemokines in C57BL/6 mice. Histology showed that sulforaphane treatment significantly prevented the eruption of endothelial lining in the intima layer of the aorta and preserved elastin fibers' delicate organization as shown by Verhoeff-van Gieson staining. Immunohistochemistry studies showed that sulforaphane treatment also reduced VCAM-1 and monocytes-derived F4/80-positive macrophages in the aorta of TNF-α-treated mice. In conclusion, sulforaphane at physiological concentrations protects against TNF-α-induced vascular endothelial inflammation, in both in vitro and in vivo models. This anti-inflammatory effect of sulforaphane may be, at least in part, associated with interfering with the NF-κB pathway.
It has been two decades since the discovery that pro-inflammatory cytokines are expressed in obesity. This initial work was the catalyst for the now-accepted paradigm that nutrient overload promotes inflammation and links the metabolic and immune systems, where inflammation may be pathological. However, inflammation is an adaptive and, importantly, an energy-consuming process. Indeed, the rapid mobilization of stored energy reserves by cytokines such as the interleukins, is critical to mounting any successful inflammatory response. Thus, the role of the interleukins in metabolism and energy homeostasis is more complex than first thought and recent evidence is mounting that, for several interleukins, although excess production is negative, blockade or insufficiency is equally undesirable.
Significance
Estrogens control the growth and development of the majority of breast cancers, the most prevalent malignancies of women in the developed world. Exemestane, a synthetic steroid commonly used clinically to prevent, delay progression of, and treat breast cancer, was designed to inhibit estrogen biosynthesis by aromatase. We have made the unexpected observation that exemestane also has widespread protective activities unrelated to blocking estrogens. Thus, exemestane is potently anti-inflammatory and antioxidant and can thereby protect against development of cancer and chronic degenerative diseases. Moreover, these activities are synergistic with sulforaphane and other cytoprotective phytochemicals. Use of such combinations could therefore provide a valuable strategy for reducing the risk of a variety of other malignancies and age-related chronic diseases.
Macrophages, and more broadly inflammation, have been considered for a long time as bad markers of tissue homeostasis. However, if it is indisputable that macrophages are associated with many diseases in a deleterious way, new roles have emerged, showing beneficial properties of macrophages during tissue repair and regeneration. This discrepancy is likely due to the high plasticity of macrophages, which may exhibit a wide range of phenotypes and functions depending on their environment. Therefore, regardless of their role in immunity, macrophages play a myriad of roles in the maintenance and recovery of tissue homeostasis. They take a major part in the resolution of inflammation. They also exert various effects of parenchymal cells, including stem and progenitor cell, of which they regulate the fate. In the present review, few examples from various tissues are presented to illustrate that, beyond their specific properties in a given tissue, common features have been described that sustain a role of macrophages in the recovery and maintenance of tissue homeostasis.
Advancing our understanding of mechanisms of immune regulation in allergy, asthma, autoimmune diseases, tumor development, organ transplantation, and chronic infections could lead to effective and targeted therapies. Subsets of immune and inflammatory cells interact via ILs and IFNs; reciprocal regulation and counter balance among T(h) and regulatory T cells, as well as subsets of B cells, offer opportunities for immune interventions. Here, we review current knowledge about ILs 1 to 37 and IFN-γ. Our understanding of the effects of ILs has greatly increased since the discoveries of monocyte IL (called IL-1) and lymphocyte IL (called IL-2); more than 40 cytokines are now designated as ILs. Studies of transgenic or knockout mice with altered expression of these cytokines or their receptors and analyses of mutations and polymorphisms in human genes that encode these products have provided important information about IL and IFN functions. We discuss their signaling pathways, cellular sources, targets, roles in immune regulation and cellular networks, roles in allergy and asthma, and roles in defense against infections.
The nuclear factor NF-kappaB pathway has long been considered a prototypical proinflammatory signaling pathway, largely based on the role of NF-kappaB in the expression of proinflammatory genes including cytokines, chemokines, and adhesion molecules. In this article, we describe how genetic evidence in mice has revealed complex roles for the NF-kappaB in inflammation that suggest both pro- and anti-inflammatory roles for this pathway. NF-kappaB has long been considered the "holy grail" as a target for new anti-inflammatory drugs; however, these recent studies suggest this pathway may prove a difficult target in the treatment of chronic disease. In this article, we discuss the role of NF-kappaB in inflammation in light of these recent studies.
Inflammatory responses play decisive roles at different stages of tumor development, including initiation, promotion, malignant conversion, invasion, and metastasis. Inflammation also affects immune surveillance and responses to therapy. Immune cells that infiltrate tumors engage in an extensive and dynamic crosstalk with cancer cells, and some of the molecular events that mediate this dialog have been revealed. This review outlines the principal mechanisms that govern the effects of inflammation and immunity on tumor development and discusses attractive new targets for cancer therapy and prevention.
Tumor necrosis factor-alpha (TNF-alpha) is a central regulator of inflammation, and TNF-alpha antagonists may be effective in treating inflammatory disorders in which TNF-alpha plays an important pathogenetic role. Recombinant or modified proteins are an emerging class of therapeutic agents. To date, several recombinant or modified proteins which acts as TNF antagonists have been disclosed. In particular, antibodies that bind to and neutralise TNF have been sought as a means to inhibit TNF activity. Inhibition of TNF has proven to be an effective therapy for patients with rheumatoid arthritis and other forms of inflammatory disease including psoriasis, psoriatic arthritis, and ankylosing spondylitis, inflammatory bowel disease. Additionally, the efficacy of preventing septic shock and AIDS has been questioned as a result of recent research. The currently available therapies include a soluble p75 TNF receptor:Fc construct, etanercept, a chimeric monoclonal antibody, infliximab, and a fully human monoclonal antibody, adalimumab. Certolizumab pegol is a novel TNF inhibitor which is an antigen-binding domain of a humanized TNF antibody coupled to polyethylene glycol (PEG) to increase half-life, and thus is Fc-domain-free. In this review, we discuss briefly the present understanding of TNF-alpha-mediated biology and the current therapies in clinical use, and focus on some of the new therapeutic approaches with small-molecule inhibitors. Moreover, we examine recent reports providing important insights into the understanding of efficacy of thalidomide and its analogs, as TNF-alpha activity inhibitories, especially in therapies of several inflammatory diseases within the nervous system.
Common to multiple vascular diseases, including atherosclerosis, interventional restenosis, and transplant vasculopathy, is a localized inflammatory reaction. Activated vascular smooth muscle cells (VSMC) respond to local inflammation and migrate from the media into the lumen of the vessel where they proliferate and synthesize cytokines which they respond to in an autocrine fashion, sustaining the progression of the lesion. The deleterious effects of pro-inflammatory cytokines, particularly immunomodulatory interleukins, on vascular pathophysiology and development of these maladaptive processes have been the subject of intense study. Although a great deal of attention has been given to the negative effects of pro-inflammatory cytokines and interleukins, relatively little has been reported on the potentially beneficial paracrine and autocrine effects of anti-inflammatory interleukins on the vascular response to injury. The vast majority of emphasis on secretion and function of anti-inflammatory mediators has been placed on leukocytes. Consequently, the role of non-immune cells, and direct effects of anti-inflammatory interleukins on vascular cells is poorly understood. We will review the molecular mechanisms whereby anti-inflammatory interleukins inhibit signal transduction and gene expression in inflammatory cells. We will review studies in which beneficial "indirect" effects of anti-inflammatory interleukins on progression of vascular disease are achieved by modulation of immune function. We will also present the limited studies in which "direct" effects of these interleukins on VSMC and endothelial cells dampen the vascular response to injury. We propose that expression of immunomodulatory cytokines by activated vasculature may represent an auto-regulatory feed back mechanism to promote resolution of the vascular response to injury.
The liver is believed to play a major role in the initiation of multiorgan failure, the most lethal complication in the clinical course of sepsis. Microbes and their virulence factors enter the hepatic circulation where they first activate sinusoidal endothelial cells and Kupffer cells to produce proinflammatory mediators, including TNF-alpha, IL-1, IL-6, reactive oxygen metabolites, and eicosanoids. These mediators cause not only microbial killing, but also structural and functional liver damage concerning mainly the parenchymal cells. Leukocytes are targeted to the liver sinusoids by chemoattractants and, like platelets, tether to the sinusoidal endothelial cells, which are in a procoagulant state of inflammatory activation. Clogging of the sinusoids by these cells leads to a decrease of blood flow through the sinusoids, which is further aggravated by endothelin-1 effectuating the constriction of hepatic stellate cells in the sinusoids. In contrast, both nitric oxide (NO) and carbon monoxide (CO) act as antagonists of endothelin-1 by mediating relaxation of sinusoidal vessels. By maintaining an adequate sinusoidal perfusion, both NO and CO are hepatoprotective during the early, hyperdynamic phase of sepsis characterized by an increased cardiac output and moderate peripheral vasodilation. However, during the late, hypodynamic phase of sepsis, massive overproduction of NO by the inducible NO synthase leads to circulatory collapse, which inevitably includes breakdown of the liver circulation.
The activation of Kupffer cells represents a central mechanism of inflammatory liver injury involving the production of two important inflammatory mediators, nitric oxide and TNF-alpha. The aim of this study was to investigate the effect of the hepatoprotective compound alpha-lipoic acid (thioctic acid) on the production of nitric oxide and TNF-alpha in isolated rat Kupffer cells and RAW 264.7 macrophages. Isolated rat Kupffer cells or RAW 264.7 were either untreated, treated with alpha-lipoic acid (500 micro g/mL), or activated with 1 micro g/mL of lipopolysaccharide in the presence or absence of alpha-lipoic acid (0.2-500 micro g/mL). After 20 h the accumulation of nitrite was measured by the Griess assay. Tumour necrosis factor-alpha secretion was quantified after 4 h by L929 bioassay. Cell viability was determined by mitochondrial reduction of 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide (MTT) test, nuclear factor-kappaB (NF-kappaB) and activator protein-1 (AP-1) DNA binding activity by gelshift assays. Treatment of Kupffer cells and RAW 264.7 with alpha-lipoic acid alone had no effect on basal nitric oxide production. However, alpha-lipoic acid significantly inhibited lipopolysaccharide-induced nitrite accumulation. alpha-Lipoic acid did not alter basal TNF-alpha secretion in Kupffer cells, whereas it significantly inhibited lipopolysaccharide-induced TNF-alpha production. alpha-Lipoic acid attenuated the activation of nuclear factor-kappaB and AP-1, two transcription factors pivotal in induction of inducible nitric oxide synthase and TNF-alpha. alpha-Lipoic acid significantly inhibits lipopolysaccharide-induced macrophage production of nitric oxide and TNF-alpha via an attenuated activation of NF-kappaB and activator protein-1. The reduced production of nitric oxide and TNF-alpha in Kupffer cells may be involved in the hepatoprotective action conveyed by alpha-lipoic acid.
TNF was originally described as a circulating factor that can cause necrosis of tumours, but has since been identified as a key regulator of the inflammatory response. This review describes the known signalling pathways and cell biological effects of TNF, and our understanding of the role of TNF in human disease. TNF interacts with two different receptors, designated TNFR1 and TNFR2, which are differentially expressed on cells and tissues and initiate both distinct and overlapping signal transduction pathways. These diverse signalling cascades lead to a range of cellular responses, which include cell death, survival, differentiation, proliferation and migration. Vascular endothelial cells respond to TNF by undergoing a number of pro-inflammatory changes, which increase leukocyte adhesion, transendothelial migration and vascular leak and promote thrombosis. The central role of TNF in inflammation has been demonstrated by the ability of agents that block the action of TNF to treat a range of inflammatory conditions, including rheumatoid arthritis, ankylosing spondylitis, inflammatory bowel disease and psoriasis. The increased incidence of infection in patients receiving anti-TNF treatment has highlighted the physiological role of TNF in infectious diseases.
- D Male
- J Brostoff
- D B Roth
- I Roitt
Male D, Brostoff J, Roth DB, Roitt I (2006) Immunology. Elsevier Canada.
Mechanism of action of nonsteroidal antiinfl ammatory drugs for the prevention of Alzheiimer's disease. CNS and neurological disorders drug targets 9
- Gm Cole
- Sa Frautschy
Cole GM, Frautschy SA (2010) Mechanism of action of nonsteroidal antiinfl ammatory drugs for the prevention of Alzheiimer's disease. CNS and
neurological disorders drug targets 9: 140-148.
Sulforaphane reduces vascular infl ammation in mice and prevents TNF-α-induced monocytes adhesion to primary endothelial cells through interfering with the NF-КB pathway
- P Nallasamy
- H Si
- Pva Babu
- D Pan
- Y Fu
Nallasamy P, Si H, Babu PVA, Pan D, Fu Y, et al. (2014) Sulforaphane reduces
vascular infl ammation in mice and prevents TNF-α-induced monocytes
adhesion to primary endothelial cells through interfering with the NF-КB
pathway. Journal of Nutritional Biochemistry 25: 824-833.
Biological functions of tumor necrosis factor cytokines and their receptors
- K Pfeiffer
Pfeiffer K (2003) Biological functions of tumor necrosis factor cytokines and
their receptors. Cytokine Growth Factor Reviews 14: 185-191.
Tumor necrosis factor signaling
- H Wajant
- K Pfi Zenmaier
- P Scheurich
Wajant H, Pfi zenmaier K, Scheurich P (2003) Tumor necrosis factor signaling.
Cell Death and Differentiation 10: 45-65.
Infl ammation, a Key Event in Cancer Development
- H Lu
- W Ouyang
- C Huwang
Lu H, Ouyang W, Huwang C (2006) Infl ammation, a Key Event in Cancer
Development. Molecular Cancer Research 4: 221-233.
Infl ammatory Mechnisms: the Molecular Basis of Infl ammation and Disease
- P Libby
Libby P (2007) Infl ammatory Mechnisms: the Molecular Basis of Infl ammation
and Disease. Nutrition Reviews.
Electrical Properties of
- Jd Lee
- A Kulkarni
- T Kim
- Gw Bahang
- Sj Moh
Lee JD, Kulkarni A, Kim T, Bahang GW, Moh SJ, et al. (2014) Electrical
Properties of " Quantum Energy ® Radiating Material " Produced from Natural
Clay Minerals of South Korea. Materials Focus 3: 1-5.
The Nuclear Factoy NF-КB Pathway in Infl ammation
- T Lawrence
Lawrence T (2009) The Nuclear Factoy NF-КB Pathway in Infl ammation. Cold
Spring Harbor Perspectives in Biology 1: a001651.
Electrical Properties of "Quantum Energy ® Radiating Material
- J D Lee
- A Kulkarni
- T Kim
- G W Bahang
- S J Moh
Lee JD, Kulkarni A, Kim T, Bahang GW, Moh SJ, et al. (2014) Electrical
Properties of "Quantum Energy ® Radiating Material" Produced from Natural
Clay Minerals of South Korea. Materials Focus 3: 1-5.
- S I Grivennikov
- F R Greten
- M Karin
Grivennikov SI, Greten FR, Karin M (2010) Immunity, Infl ammation, and
Cancer. Cell 140: 883-889.
High-Resolution Transcriptome of Human Macrophages
- M Beyer
- M R Mallman
- J Xue
- A Saratschek-Jox
- D Vorholt
Beyer M, Mallman MR, Xue J, Saratschek-Jox A, Vorholt D, et al. (2012) High-Resolution Transcriptome of Human Macrophages.
Mechanism of action of nonsteroidal antiinfl ammatory drugs for the prevention of Alzheiimer's disease. CNS and neurological disorders drug targets
- G M Cole
- S A Frautschy
Cole GM, Frautschy SA (2010) Mechanism of action of nonsteroidal antiinfl ammatory drugs for the prevention of Alzheiimer's disease. CNS and
neurological disorders drug targets 9: 140-148.