Search results for "Inflammation."
showing 10 items of 2627 documents
Epithelial-mesenchymal communication in the pathogenesis of chronic asthma.
2005
Although Th-2-mediated inflammation is a key therapeutic target in asthma, its relationship to altered structure and functions of the airways is largely unknown. In addition to inflammation, asthma is a disorder involving the airway epithelium that is more vulnerable to environmental injury and responds to this by impaired healing. This establishes a chronic wound scenario that is capable of sustaining chronic inflammation as well as remodeling. This response occurs as a consequence of activation of the epithelial-mesenchymal unit, involving reciprocal activities of growth factors belonging to the fibroblast growth factor, epidermal growth factor, and transforming growth factor-beta familie…
Nanocomplexes for gene therapy of respiratory diseases: Targeting and overcoming the mucus barrier
2015
Gene therapy, i.e. the delivery and expression of therapeutic genes, holds great promise for congenital and acquired respiratory diseases. Non-viral vectors are less toxic and immunogenic than viral vectors, although they are characterized by lower efficiency. However, they have to overcome many barriers, including inflammatory and immune mediators and cells. The respiratory and airway epithelial cells, the main target of these vectors, are coated with a layer of mucus, which hampers the effective reaching of gene therapy vectors carrying either plasmid DNA or small interfering RNA. This barrier is thicker in many lung diseases, such as cystic fibrosis. This review summarizes the most impor…
Future Directions in the Pharmacologic Therapy of Chronic Obstructive Pulmonary Disease
2005
Current therapy for chronic obstructive pulmonary disease (COPD) fails to alter its relentless progression. This remains a significant challenge and unmet need. A recent advance is the demonstration that treatment with a fixed dose of an inhaled corticosteroid and a long-acting beta2-agonist in COPD improves lung function and quality of life, and reduces exacerbation more effectively than either drug alone. Other improvements include the introduction of tiotropium, a once-daily anticholinergic. In advanced clinical development are other once-daily bronchodilators and combinations of anticholinergic drugs and beta2-agonists. Increased understanding of the pathogenesis of COPD has led to nove…
Lung penetration and patient adherence considerations in the management of asthma: role of extra fine formulations
2013
The mainstay of management in asthma is inhalation therapy at the target site, with direct delivery of the aerosolized drug into the airways to treat inflammation and relieve obstruction. Abundant evidence is available to support the concept that inflammatory and functional changes at the level of the most peripheral airways strongly contribute to the complexity and heterogeneous manifestations of asthma. It is now largely accepted that there is a wide range of clinical phenotypes of the disease, characterized primarily by small airways involvement. Thus, an appropriate diagnostic algorithm cannot exclude biological and functional assessment of the peripheral airways. Similarly, achievement…
Zur Immunpathogenese des Asthma bronchiale
2000
Allergic asthma is a chronic pulmonary disease associated with bronchoconstriction and inflammation. Recent studies have shown that mediator substances and proinflammatory cytokines produced by mast cells, eosinophils and T-lymphocytes appear to be important for the pathogenesis of asthma. These substances contribute both to the initiation and perpetuation of the disease. In particular, it has been shown that allergic asthma is associated with increased TH2 (IL-4, IL-5, IL-13) cytokine production that causes activation of eosinophils and T-cells and production of chemokines (e.g. eotaxin) by pulmonary fibroblasts. Based on recent advances in our understanding of the immunopathogenesis of as…
Interleukin-2 receptor gene expression by bronchoalveolar lavage lymphocytes in pulmonary sarcoidosis.
1989
Current concepts of the immunopathogenesis of sarcoidosis favor a central role of activated, interleukin-2 (IL-2) producing helper T-cells at sites of inflammation. Normally, activated T-cells release IL-2 and express IL-2 receptors (IL-2R). IL-2R+ cells, however, are not uniformly found in patients with clinically active disease. To determine whether the lack of IL-2R+ cells is caused by a dysregulation of the IL-2R gene or by the mode of T-cell activation in pulmonary sarcoidosis, we quantified IL-2 and IL-2R m-RNA transcripts, IL-2 release, and IL-2R surface protein in peripheral blood lymphocytes of patients with sarcoidosis and normal control subjects before and after in vitro stimulat…
Lung-restricted activation of the alveolar macrophage/monocyte system in pulmonary sarcoidosis.
1992
An activation of T-cells that is restricted to the lung has been demonstrated in pulmonary sarcoidosis. The role of blood monocytes (MO) and alveolar macrophages (AM) in this concept of compartmentalized inflammation has not yet been evaluated. In order to elucidate this question, we measured the release of tumor necrosis factor alpha (TNF alpha) and interleukin-1 (IL-1) by peripheral blood mononuclear cells (PBMNC) and AM in 43 patients with sarcoidosis (32 with active, 11 with inactive disease) without therapy and correlated the spontaneous monokine release to parameters of the T-cell alveolitis and the course of the disease. TNF alpha as well as IL-1 were spontaneously released by AM of …
Modulation of endotoxin-induced neutrophil transendothelial migration by alveolar epithelium in a defined bilayer model.
2006
Within the alveolus, epithelial cells, due to their close association with endothelial cells, can potentially influence endothelial cell responsiveness during inflammation and their interaction with leukocytes. To investigate this, three lung epithelial cell lines (A549, Calu-3, or NCI-H441) were grown with endothelium on opposing surfaces of Transwell filters and the formation and stability of bilayers was rigorously evaluated. All epithelial lines disrupted endothelial monolayer formation on filters with 3- or 5-microm pores by breaching the filter, and this occurred regardless of seeding density, matrix composition, or duration of culture. Endothelial disruption was not detectable by ele…
The Non-neuronal cholinergic system: an emerging drug target in the airways.
2001
The non-neuronal cholinergic system is widely expressed in human airways. Choline acetyltransferase (ChAT) and/or acetylcholine are demonstrated in more or less all epithelial surface cells (goblet cells, ciliated cells, basal cells), submucosal glands and airway smooth muscle fibres. Acetylcholine is also demonstrated in the effector cells of the immune system (lymphocytes, macrophages, mast cells). Epithelial, endothelial and immune cells express nicotinic and muscarinic receptors. Thus the cytomolecule acetylcholine can contribute to the regulation of basic cell functions via auto-/paracrine mechanisms (proliferation, differentiation, ciliary activity, secretion of water, ions and mucus,…
Obstructive sleep apnoea in acute coronary syndrome.
2019
Obstructive sleep apnoea (OSA) syndrome affects about 13% of the male and 7–9% of the female population. Hypoxia, oxidative stress and systemic inflammation link OSA and cardiovascular and metabolic consequences, including coronary artery disease. Current research has identified several clinical phenotypes, and the combination of breathing disturbances during sleep, systemic effects and end-organ damage might help to develop personalised therapeutic approaches. It is unclear whether OSA is a risk factor for acute coronary syndrome (ACS) and might affect its outcome. On the one hand, OSA in patients with ACS may worsen prognosis; on the other hand, OSA-related hypoxaemia could favour the dev…