Search results for "Toll-Like Receptors"
showing 10 items of 70 documents
Regulation of T cells in asthma: implications for genetic manipulation
2004
PURPOSE OF THE REVIEW Allergic asthma is a disease characterized by airway hyperresponsiveness, inflammation and remodeling. In the past few decades it has become clear that the pathogenesis and development of this disease is controlled by cytokines released by CD4 T helper type 2 lymphocytes that develop under the influence of natural killer lymphocytes. At birth, T cell priming exhibits a T helper type 2 bias and the development of the T helper phenotype is determined in the first year of life by environmental exposure to virus or bacterial substances or environmental allergens in genetically predisposed individuals. Decreased exposure to infection in early childhood has thus been linked …
Immunity, Inflammation and Heart Failure. Their Role on Cardiac Function and Iron Status
2019
Aims: Heart failure is a clinical syndrome characterized by subclinical systemic inflammation and immune system activation associated with iron deficiency. No data exist on the various activations of immune-mediated mechanisms of inflammation in heart failure patients with reduced/preserved ejection fraction. We aimed to (1) investigate possible differences in inflammatory parameters and oxidative stress, and (2) detect a different iron status between groups. Materials and Methods: We enrolled 50 consecutive Caucasian outpatients with heart failure. All patients underwent echocardiographic measurements, laboratory determinations, evaluation of iron status and Toll-like receptors, and NF-κB …
Molecular basis of endothelial dysfunction in sepsis.
2003
Sepsis is one of the major causes of mortality in critically ill patients and develops as a result of the host response to infection. A complex network of events is set into motion in the body by the infection and results in the pathogenesis of sepsis. This review article focuses on the molecular mechanisms and components involved in the pathogenesis of sepsis with a major emphasis on the endothelium. This includes sepsis-inducing bacterial components (e.g. endotoxins), cellular targets of these molecules and their responses, host reactions, intracellular and cytokine networks, individual susceptibility and new therapeutic targets in sepsis treatment.
Partial Sleep Restriction Activates Immune Response-Related Gene Expression Pathways: Experimental and Epidemiological Studies in Humans
2013
Epidemiological studies have shown that short or insufficient sleep is associated with increased risk for metabolic diseases and mortality. To elucidate mechanisms behind this connection, we aimed to identify genes and pathways affected by experimentally induced, partial sleep restriction and to verify their connection to insufficient sleep at population level. The experimental design simulated sleep restriction during a working week: sleep of healthy men (N = 9) was restricted to 4 h/night for five nights. The control subjects (N = 4) spent 8 h/night in bed. Leukocyte RNA expression was analyzed at baseline, after sleep restriction, and after recovery using whole genome microarrays complem…
Influence of aging on murine neutrophil and macrophage function against Candida albicans.
2008
Previous work by our group showed that aged C57BL/6 mice develop an altered innate and adaptive immune response to Candida albicans and are more susceptible to systemic primary candidiasis. In this work, we used young (2-3 months old) and aged (18-20 months old) C57BL/6 mice to study in vitro the influence of aging on (1) the fungicidal activity of neutrophils and macrophages, (2) the production of cytokines by resident peritoneal macrophages in response to C. albicans, and (3) cell surface Toll-like receptor (TLR) 2 expression on resident peritoneal macrophages. Our results indicate that murine phagocytes have a fungicidal activity well preserved with aging. In vitro production of proinfla…
Recent Advances on the Innate Immune Response to Coxiella burnetii.
2021
Coxiella burnetii is an obligate intracellular Gram-negative bacterium and the causative agent of a worldwide zoonosis known as Q fever. The pathogen invades monocytes and macrophages, replicating within acidic phagolysosomes and evading host defenses through different immune evasion strategies that are mainly associated with the structure of its lipopolysaccharide. The main transmission routes are aerosols and ingestion of fomites from infected animals. The innate immune system provides the first host defense against the microorganism, and it is crucial to direct the infection towards a self-limiting respiratory disease or the chronic form. This review reports the advances in understanding…
Cutting Edge: IL-1α Is a Crucial Danger Signal Triggering Acute Myocardial Inflammation during Myocardial Infarction
2016
Abstract Myocardial infarction (MI) induces a sterile inflammatory response that contributes to adverse cardiac remodeling. The initiating mechanisms of this response remain incompletely defined. We found that necrotic cardiomyocytes released a heat-labile proinflammatory signal activating MAPKs and NF-κB in cardiac fibroblasts, with secondary production of cytokines. This response was abolished in Myd88−/− fibroblasts but was unaffected in nlrp3-deficient fibroblasts. Despite MyD88 dependency, the response was TLR independent, as explored in TLR reporter cells, pointing to a contribution of the IL-1 pathway. Indeed, necrotic cardiomyocytes released IL-1α, but not IL-1β, and the immune acti…
Redox signaling in acute pancreatitis
2015
Acute pancreatitis is an inflammatory process of the pancreatic gland that eventually may lead to a severe systemic inflammatory response. A key event in pancreatic damage is the intracellular activation of NF-κB and zymogens, involving also calcium, cathepsins, pH disorders, autophagy, and cell death, particularly necrosis. This review focuses on the new role of redox signaling in acute pancreatitis. Oxidative stress and redox status are involved in the onset of acute pancreatitis and also in the development of the systemic inflammatory response, being glutathione depletion, xanthine oxidase activation, and thiol oxidation in proteins critical features of the disease in the pancreas. On th…
TLR4 Up-regulation and Reduced Foxp3 Expression in Mechanically Ventilated Smokers with Obstructive Chronic Bronchitis
2013
Background: Chronic bronchitis (CB) is a risk factor in chronic obstructive pulmonary disease (COPD) for accelerated lung function decline and increased mortality. The lung and systemic inflammatory and immunological profile of COPD patients with CB which acutely experience respiratory failure upon a disease exacerbation is unknown. Methods: In this study, we explored the expression of Foxp3 by western blot analysis, TLR4 by immunocytochemistry and the concentrations of IP-10 and IL-8 by ELISA in the mini-bronchoalveolar lavages (mini-BAL) and in the peripheral blood of patients with respiratory failure requiring intubation and mechanical ventilation. The recruited subjects were separated i…
EBV-Induced Gene 3 Transcription Is Induced by TLR Signaling in Primary Dendritic Cells via NF-κB Activation
2005
Abstract The EBV-induced gene 3 (EBI3) is expressed in dendritic cells (DCs) and part of the cytokine IL-27 that controls Th cell development. However, its regulated expression in DCs is poorly understood. In the present study we demonstrate that EBI3 is expressed in splenic CD8−, CD8+, and plasmacytoid DC subsets and is induced upon TLR signaling. Cloning and functional analysis of the EBI3 promoter using in vivo footprinting and mutagenesis showed that stimulation via TLR2, TLR4, and TLR9 transactivated the promoter in primary DCs via NF-κB and Ets binding sites at −90 and −73 bp upstream of the transcriptional start site, respectively. Furthermore, we observed that NF-κB p50/p65 and PU.1…