Toll-Like Receptors 2 and 4 Agonists Activate Airway Smooth Muscle via Mononuclear Leukocytes

Toll-Like Receptors
Toll-like receptors (TLRs) act as receptors for numerous stimuli of immune cells, including bacterial cell wall constituents (lipopolysaccharide [LPS] from Gram-negative bacteria and lipopeptides from Gram-positive species), plasma proteins and extracellular matrix breakdown products. TLR2 and TLR4 bind lipopeptide and LPS respectively, mediating responses of alveolar macrophages and other immune cells to bacterial infection in the lungs. Exposure of lungs to LPS leads to pro-inflammatory responses of a number of cell types, including airway smooth muscle, which secretes a number of cytokines involved in leucocyte recruitment and the Th2 polarization of immune responses. Human airway smooth muscle cells were cultured with LPS in the absence and presence of peripheral blood mononuclear cells to determine direct and leucocyte-dependent TLR-mediated responses. (more…)

IL-6 Inhibitor Induction in Coculture Of Bronchial Epithelial Cells and Eosinophils

IL-6 Inhibitor
Eosinophil infiltration of the mucosa is a feature of asthmatic airways. Their adhesion to bronchial epithelial cells has been proposed to lead to the generation of inflammation mediators which may contribute to asthma pathology. Bronchial epithelial cells (BEAS-2B cell line) and peripheral blood eosinophils were cultured alone or in combination and the production of an inflammatory cytokine, IL-6, was measured. IL-6 was produced principally by epithelial cells and the production was enhanced more than 10-fold in the presence of eosinophils. Significant augmentation of epithelial IL-6 production persisted even when eosinophils were fixed with paraformaldehyde. The eosinophil-induced IL-6 production was extensively inhibited by inhibitors of p38 mitogen-activated protein (MAP) kinase or nuclear factor ??B (NF??B). (more…)

Montelukast Side Effects as Antileukotrienes Therapy to Inhaled Corticosteroids in Asthma

antileukotrienes therapy
Despite optimum drug delivery and good compliance with inhaled corticosteroids, many patients experience symptoms and exacerbations. Dose–response studies using inhaled corticosteroids have generally been unable to demonstrate any significant difference between individual doses of inhaled corticosteroids. For example, a metaanalysis evaluated eight studies (2324 asthmatics) where the effects of at least two doses of inhaled fluticasone were measured. (more…)

Treg Cells In Allergen-Specific Immunotherapy

treg cells
Treg cells or regulatory T cells constitute a large population of cellular infiltrate in atopic/allergic inflammation and a dysregulated immune response appears to be an important pathogenetic factor. Cardinal events during allergic inflammation can be classified as activation, organ-selective homing, survival and reactivation, and effector functions of immune system cells. T cells are activated by aeroallergens, food antigens, autoantigens, and bacterial exotoxins superantigens in allergic inflammation. They are under the influence of the skin, lung, or nose-related chemokine network and show organ-selective homing. (more…)

Foxp3 Forkhead Winged Transcription Factor & Mechanisms Of Suppression

foxp3
The intracellular forkhead winged transcription factor Foxp3 (forkhead box P3) appears to be specifically expressed by naturally occurring Treg cells, particularly in mice, although in humans there is evidence of upregulation of Foxp3 in all T cells on activation. Foxp3 is required for the development and function of naturally occurring regulatory t cells (treg) and expression is sufficient to convert non-regulatory CD4+CD25T cells into cells with regulatory activity. Conversion of peripheral CD4+CD25 naive T cells to Foxp3+CD4+CD25 foxp3+ Treg cells can be induced by TGF-ß. In a murine asthma model, these TGF-ß-induced Treg prevented house-dust mite-induced allergic pathogenesis or infection pathogenesis in lungs. A single independent report has suggested that IL-4 and IL-13 also induce Foxp3+CD25+ Treg from CD4+CD25precursors. (more…)

Antileukotriene Drugs for Airway Hyperresponsiveness & Asthma Treatment

antileukotriene
A variety of proinflammatory cells, mediators, and cytokines orchestrate the development of airway hyperresponsiveness, which results in the episodic airflow obstruction characteristic of asthma. As a consequence, modulation of the underlying disease process with antii-nflammatory agents is firmly established as being the cornerstone of successful management. Inhaled corticosteroids are the most potent antiinflammatory agents available and satisfactorily suppress underlying airway inflammation in most individuals. (more…)

Tumour Necrosis Factor Effects on Antagonism On Allergen-Mediated Asthmatic Airway Inflammation

Tumour Necrosis Factor is a pro-inflammatory cytokine implicated in the pathogenesis of asthmatic airway inflammation, hyper-reactivity and remodelling. The primary aim of the trial was to assess whether TNF antagonism, using a soluble Tumour Necrosis Factor receptor (TNFR:Fc etanercept, Enbrel ® ), can attenuate eosinophilic airway inflammation in patients with mild to moderate allergic asthma. (more…)

Mite Allergen-Impermeable Bed-Covering System Effectiveness In Asthmatic Mite-Sensitive Patients

Allergen exposure plays a role in the development of asthma bronchial hyper-responsiveness and in the acute inflammatory response seen in asthmatic patients. Reduction of house dust mite allergens might lead to better lung function and reduction of asthma symptoms. (more…)

Vascular Endothelial Growth Factor (VEGF) & Induces Muscle Hyperflasia Enhances TH2-Mediated Sensitization

Vascular Endothelial Growth Factor (VEGF), originally described as a vascular permeability factor generating tissue oedema, has been found to exert a range of angiogenic actions, including epithelial cell proliferation, blood vessel formation and endothelial cell survival. Elevated levels of Vascular Endothelial Growth Factor have been detected in bronchial tissues and secretions of asthmatic bronchial individuals, raising questions regarding its possible pathogenetic role in asthma. Using transgenic mice in which local over expression of VEGF could be induced in the lungs by administration of a tetracycline antibiotic demonstrated induction of an asthma-like phenotype with airway inflammation and oedema, hyper-responsiveness and remodelling (airway, parenchymal and vascular). Antigen-induced airway inflammation was accompanied by VEGF production by epithelial cells and TH2 cells, with production by Th1 cells markedly lower. (more…)

Asthma With Concomitant Allergic Rhinitis Among Asthmatic Children

Asthmatic children who also have Allergic Rhinitis seem to have higher morbidity and to use more healthcare resources. This was further investigated to determine the incremental effect of Allergic Rhinitis on healthcare resource use in children with asthma. The data were from a general practice database in the UK and covered the period 1998–2001. Children aged 6–15 years who had an asthma related visit to their general practitioner at least once during a defined 12 month period were reviewed. (more…)

Next Page »