The epithelium constitutes the interface between the internal milieu and the external environment, and the nasal epithelium is the initial point of contact for respiratory viruses, airborne allergens and environmental pollutants. The major function of the nasal epithelium was regarded to be primarily that of a physical barrier, but recent ...

T lymphocyte apoptosis is essential for maintaining immune system homeostasis. Experimental evidence suggests apoptosis control mechanisms may be impaired in inflammatory conditions, particularly airway Th2-type allergic diseases. This review briefly examines the mucosal immune system homeostasis and common apoptotic pathways and discusses impaired apoptosis, allergy, airway inflammation, remodelling and fibrosis. ...

The aim of this thesis was to investigate both the early and late effects of cigarette smoke and nitrogen dioxide (NO2) exposure and the potential dampening effects of heme oxygenase-1 (HO-1) in animal models for COPD. Additionally, we investigated the role of the specific immune response in the inflammatory response ...

BACKGROUND: Airway epithelial cells not only constitute a physical barrier, but also the first line of defence against airborne pathogens. At the same time, they are constantly exposed to reactive oxygen species. Therefore, airway epithelia cells have to possess a sophisticated innate immune system and a molecular armamentarium to detoxify ...

Interest in regulatory T cells (Treg) and their role in immune regulation has grown almost exponentially over the last 10 years, though the notion of a suppressive population of T cells has been in existence since the early 1970s. Recent reports have highlighted the potential role of populations of Treg ...

IL-17 is a proinflammatory cytokine produced by immune cells. Its significance in host defense and disease development has been demonstrated in various infection and autoimmune models. Recently, additional studies have shown that IL-17 is also important in modulating airway immune response in several aspects. Along with the well-established Th1/Th2 model, ...

The airway epithelium represents a primary site for the introduction and deposition of potentially pathogenic microorganisms into the body, through inspired air. The epithelial mucosa is an important component of the innate immune system that recognizes conserved structures in microorganisms and initiates appropriate signaling to recruit and activate phagocytic cells ...

BACKGROUND: Smoking alters the inflammatory cell balance in the airways, often leading to repeated respiratory infections and, eventually, chronic obstructive pulmonary disease (COPD) in susceptible individuals. OBJECTIVE: It was the aim of this study to evaluate alterations in the airway inflammatory balance caused by chronic cigarette smoke exposure. METHODS: We ...

Counter-regulatory lipid mediators are generated during airway inflammation to promote resolution. Defects in the production of these lipid mediators have now been associated with several diseases of persistent airway inflammation. Lipoxins are the lead members of this class of anti-inflammatory and proresolving chemical mediators. Recently, several new families of fatty ...

BACKGROUND: Allergic asthma is caused by aberrant helper T (T(H)) type 2 immune responses in susceptible individuals, characterized by airway hyperresponsiveness, chronic airway inflammation, and mucus hypersecretion. Its prevalence continues to increase, but optimal treatment remains a challenge. The transcription factor T-bet is a master regulator of T(H)1 lineage commitment ...

Cell-penetrating peptides (CPPs) or protein transduction domains (PTDs) are peptides that have the ability to efficiently traverse cellular membranes, either alone or in association with molecular cargo. Several naturally occurring PTDs, including those from HIV TAT and Drosophila antennapedia, have this unique activity. Synthetic CPPs, such as polyarginine, also have ...

T cells are critical mediators of the allergic airway inflammation seen in asthma. Pathogenic allergen-specific T cells are generated in regional lymph nodes and are then recruited into the airway by chemoattractants produced by the asthmatic lung. These recruited effector T cells and their products then mediate the cardinal features ...

Cystic fibrosis (CF) is the most common lethal monogenic disorder in Caucasians, estimated to affect one out of 2500-4000 new-borns. In patients with CF, lack of CF transmembrane conductance regulator (CFTR) Cl(-) channel function leads to progressive pulmonary damage and ultimately to death. Severe and persistent polymorphonuclear neutrophil-dominated endobronchial inflammation ...

Asthma is a chronic inflammatory disease of the airways, involving recurrent episodes of airway obstruction and wheezing. A common pathological feature in asthma is the presence of a characteristic allergic airway inflammatory response involving extensive leukocyte infiltration, mucus overproduction and airway hyper-reactivity. The pathogenesis of allergic airway inflammation is complex, ...

BACKGROUND: In asthma, mechanisms contributing to chronicity remain to be determined. Recent models of sensitisation with prolonged airway allergen challenges reproduce typical features of chronic asthma. However, the interplay between inflammation, structural changes and lung function is poorly understood. This study was performed to delineate functional, structural and immunological airway ...

INTRODUCTION: Inflammation is a core feature of acute chronic obstructive pulmonary disease (COPD) exacerbations. It is important to focus on inflammation since it gives insight into the pathological changes causing an exacerbation, thereby possibly providing directions for future therapies which modify inflammation. OBJECTIVES: To provide a cell-by-cell overview of the ...

Thymic stromal lymphopoietin (TSLP), a novel interleukin-7-like cytokine, triggers dendritic cell-mediated inflammatory responses ultimately executed by T helper cells of the Th2 subtype. TSLP emerged as a central player in the development of allergic symptoms, especially in the airways, and is a prime regulatory cytokine at the interface of virus- ...

Airway epithelium (AE) lines the conducting airways of the respiratory system and functions to maintain airway integrity by providing both a physical barrier to inhaled noxious agents and a mechanism for their clearance via the mucociliary escalator. Normal AE cells are relatively refractory to a number of apoptotic stimuli and ...

BACKGROUND: Asthma is a chronic inflammatory disease that is characterized clinically by airway hyperresponsiveness (AHR) to bronchoconstricting agents. The physiological response of the asthmatic lung to inhaled allergen is often characterized by two distinct phases: an early-phase response (EPR) within the first hour following exposure that subsides and a late-phase ...

BACKGROUND: The non-essential amino acid, l-glutamine (Gln), is abundant in the human body. Gln exhibits beneficial effects on endotoxic shock through the inhibition of cytosolic phospholipase A(2) (cPLA(2)) activity. cPLA(2) has been reported to be implicated in the pathogenesis of asthma, but the effects of Gln on asthma have not ...

Although asthma is an inflammatory disorder of the conducting airways involving T(H)2-type T cells, there is increasing evidence for an important role played by the epithelium in orchestrating the inflammatory response by interacting with multiple environmental factors to produce a chronic wound scenario involving tissue injury and aberrant repair. Part ...

Research on the biology of airway epithelium in the last decades has progressively uncovered the many roles of this cell type during the immune response. Far from the early view of the epithelial layer simply as a passive barrier, the airway epithelium is now considered a central player in mucosal ...

Nitric oxide (NO) levels are elevated in the exhaled breath of asthmatic patients and NO is considered as a biomarker of airway inflammation. However, the functions of NO in the airways are not completely understood. L-arginine, as the substrate of NO synthases, is the precursor of NO which stimulates guanylate ...

Chronic obstructive pulmonary disease (COPD) is a highly prevalent airway disease characterized by an abnormal inflammatory response of the lungs to noxious particles and gases. Cigarette smoking remains a major risk factor in COPD development. Accumulating evidence suggests that apoptosis, a regulated form of cell death, may play an important ...

Airway inflammation is a critical feature of the airway diseases asthma and chronic obstructive pulmonary disease (COPD). There is emerging evidence that structural cells play a key role in the development and perpetuation of the inflammatory response and are pivotal in the development of the changes in the airway structures ...

Airways from asthmatic subjects are more responsive to bronchoconstrictive stimuli than airways from healthy subjects. Airway smooth muscle (ASM) cells mediate contraction of the airways by responding to the bronchoconstrictive stimuli, which was thought to be the primary role of ASM cells. In this thesis, we have addressed the role ...

The aims of this study were firstly to characterise a model of subclinical and reversible bronchial inflammation induced by cadmium chloride inhalation in healthy dogs and then to examine the effect of prednisolone or salbutamol treatment on the resulting bronchitis. The model characterisation and the effects of treatment were studied ...

Bacterial flagellin, which activates Toll-like receptor 5 and cytosolic pattern recognition receptor Ipaf, has a strong immunomodulatory activity. In the present study, we examined whether intranasal co-administration of flagellin with allergen could modulate established airway hyperresponsiveness and Th2 response using an ovalbumin (OVA)-sensitized mouse model. Balb/c mice sensitized with OVA ...

One of the first lines of defence to inhaled toxins is the barrier formed by the tracheobronchial epithelium, making this the ideal region for studying the toxicity of inhaled substances. This study utilises a highly differentiated, three-dimensional, in vitro model of human upper respiratory tract epithelium (EpiAirway-100) to measure the ...

Airway mucosal dendritic cells (AMDC) and other airway APCs continuously sample inhaled Ags and regulate the nature of any resulting T cell-mediated immune response. Although immunity develops to harmful pathogens, tolerance arises to nonpathogenic Ags in healthy individuals. This homeostasis is thought to be disrupted in allergic respiratory disorders such ...

Asthma is a chronic inflammatory disease characterized by reversible airflow limitation and airway hyperresponsiveness. Persistent inflammation in airway tissues may lead to structural changes known as airway remodeling and consequently airway obstruction that is not fully reversible and progressive loss of lung function over time. It is generally accepted that ...

Nitric oxide (NO) is thought to have many regulatory roles at each stage of the development of inflammation. NO regulates many aspects of human airway biology, including the modulation of airway and vascular smooth muscle tone. It is generated from NO synthase (NOS)-1, -2 and -3, which have been detected ...

Airway remodeling can be defined as changes in the composition, content, and organization of the cellular and molecular constituents of the airway wall. Airway remodeling is a characteristic feature of asthma, and has important functional implications. These structural changes include epithelial detachment, subepithelial fibrosis, increased airway smooth muscle (ASM) mass, ...

The historical change in the natural course of diffuse panbronchiolitis (DPB), a fatal disorder of the airways, following the introduction of erythromycin in its treatment has focused attention of researchers on the anti-inflammatory properties of macrolides. Chronic inflammation of the airways accompanied by infiltration by neutrophils and overproduction of mucus ...

Asthma is a chronic airway disorder principally characterized by bronchial hyperreactivity and airflow obstruction. Increased epithelial and smooth muscle thickness, goblet cell hyperplasia, increased mucus secretion, abnormal deposition of extracellular matrix (ECM) components in the basement membrane (BM) layer and angiogenesis are all events which occur in asthma and are ...

BACKGROUND: Pathogenesis of COPD is, at least in part, attributable to the chronic accumulation of neutrophils in the airways, and morphological changes such as hyperplasia of goblet cells in the airways are often observed in this disease. These structural changes were induced in guinea pigs by repetitive inhalations of LPS, ...

Gap junction channels formed with connexins directly link to the cytoplasm of adjacent cells and have been implicated in intercellular signaling. Connexin 37 (Cx37) is expressed in the gas-exchange region of the lung. Recently, Cx37 has been reported to be involved in the pathogenesis of inflammatory disease. However, no data ...

BACKGROUND: Traditional therapies for asthma and allergic rhinitis (AR) such as corticosteroids and antihistamines are not without limitations and side effects. The use of complementary and alternative approaches to treat allergic airways disease, including the use of herbal and dietary supplements, is increasing but their efficacy and safety are relatively ...

It has become increasingly clear that airway epithelial cells are central participants in innate and adaptive immune responses as well as mucosal inflammation. Epithelial cells produce antimicrobial host defense molecules, proinflammatory cytokines and chemokines in response to activation via pathogen recognition receptors. Recruitment of immune cells including dendritic cells, T ...

BACKGROUND: RNA interference is an endogenous cellular mechanism in which short interfering RNAs (siRNAs) direct the sequence specific degradation of a target mRNA. siRNAs can be synthesized with chemical modifications to increase stability and reduce double-stranded RNA-induced immune responses without affecting their ability to elicit degradation of target mRNA. OBJECTIVES: ...

Several diseases of the airways have a strong component of allergic inflammation in their cause, including allergic rhinitis, asthma, polypoid chronic rhinosinusitis, eosinophilic bronchitis, and others. Although the roles played by antigens and pathogens vary, these diseases have in common a pathology that includes marked activation of epithelial cells in ...

BACKGROUND: Hypertonic saline (HS) has been shown to modulate in vitro cell functions according to the state of cell activation; however, few studies have evaluated the effect of HS in vivo. Chronic airway inflammation, a major feature of chronic obstructive pulmonary disease (COPD), is associated with an activation of inflammatory ...

BACKGROUND: Proteinase-activated receptors (PAR)-2 are members of the family of G-protein-coupled receptors activated by proteases. These receptors are widely expressed in several tissues and in virtually all cells involved in rhinitis and asthma. In particular, proteinases activating PAR-2 may affect airway functions and play a role in human diseases. OBJECTIVE: ...

Chronic obstructive pulmonary disease (COPD) progression is characterized by accumulation of inflammatory mucous exudates in the lumens of small airways, and thickening of their walls, which become infiltrated by innate and adaptive inflammatory immune cells. Infiltration of the airways by polymorphonuclear and mononuclear phagocytes and CD4 T cells increases with ...

BACKGROUND: Airway remodelling is a central pathophysiological feature of chronic asthma. A wide variety of cytokines and growth factors are likely to be involved in the development of airway remodelling. Osteopontin (OPN) is a cytokine with pro-fibrotic properties; however, its role in airway remodelling in asthma has not been explored. ...

Squamous metaplasia in the tracheobronchial epithelium (TBE) involves the replacement of the normal pseudostratified mucociliary epithelium with a stratified squamous epithelium. Squamous metaplasia is considered to be an adaptive response that protects the lumen from the effects of inhaled airborne pollutants, but which might also feature as a pre-neoplastic lesion ...

The allergen challenge has evolved, in less than 150 years, from a crude tool used to document the etiology of allergen-induced disease to a well-controlled tool used today to investigate the pathophysiology and pharmacotherapy of asthma. Highlights of the authors' involvement with the allergen challenge include confirmation of the immunoglobulin ...

Paper mill workers are exposed to culturable microorganisms (MOs). We hypothesized that inflammatory airway response could be detected in sputum of nonsymptomatic workers. From four paper mills, we included 29 healthy nonsmoking men. Workers exposed to high levels of MOs (HMOE, n = 17) were compared with workers exposed to ...

Airway inflammation and epithelial remodeling are two key features of asthma. IL-13 and other cytokines produced during T helper type 2 cell-driven allergic inflammation contribute to airway epithelial goblet cell metaplasia and may alter epithelial-mesenchymal signaling, leading to increased subepithelial fibrosis or hyperplasia of smooth muscle. The beneficial effects of ...

Epithelia in the human airways, from the nasal aperture to the alveoli, are covered in a protective film of fluid containing a number of antimicrobial proteins. Defensins are single-chain, strongly cationic peptides and are one of the most extensively studied classes of antimicrobial peptides. Moxifloxacin (MXF) is a fluoroquinolone that ...