Notch-1 decreased expression contributes to leptin receptor downregulation in nasal epithelium from allergic turbinates

Abstract BACKGROUND: Allergic rhinitis is characterized by a remodeling of nasal epithelium. Since the Notch and TGF-β signaling pathways are known to be involved in cell differentiation and remodeling processes and leptin adipokine has already been identified as a marker for homeostasis in human bronchial and nasal epithelial cells of asthmatics, roles played by these pathways have been investigated for chronic allergic rhinitis. METHODS: The leptin/leptin receptor expression has been investigated in a study with 40 biopsies from allergic (AR, n = 18) and non-allergic (C, n = 22) inferior turbinates, using immunohistochemistry, immunofluorescence staining and RT-PCR. In addition, extracts …

Relationship among Body Composition, Adipocytokines, and Irisin on Exercise Capacity and Quality of Life in COPD: A Pilot Study

Adipose tissue is an endocrine organ that interferes with the severity of chronic obstructive pulmonary disease (COPD). Although inflammatory markers, body composition, and nutritional status have a significant impact on pulmonary function, the real contribution of adipocytokines and myokines in COPD is still controversial. We aimed to evaluate the role played by the body composition, leptin, adiponectin, haptoglobin, and irisin on the functional exercise capacity, respiratory function, and quality of life (QoL) in COPD. In 25 COPD (20% GOLD-1; 60% GOLD-2; 20% GOLD-3) patients and 26 matched control subjects, we find that leptin, total adiponectin and haptoglobin are significantly increased…

The role of internship for the future of professional careers in psychology: an explorative study on the academic practices featuring Italian degree programmes

The significant changes envisaged by the reform related to the role of internship in the degree programmes in Psychology will have important consequences for future psychologists’ professional careers in Italy. Con- sidering the relevant guiding function played by the internship in the development of future career paths of graduates, the MeMoS group, proposed a research project aimed to investigate the state of the art of the Italian degree programmes in Psychology, collecting information about internships and their impact on fu- ture psychologists’ professionalisation. A structured interview was developed to understand the processes related to internships within the Psychology programmes i…

Leptin and TGF-β1 Downregulate PREP1 Expression in Human Adipose-Derived Mesenchymal Stem Cells and Mature Adipocytes

International audience; Adipose tissue is widely recognized as an extremely active endocrine organ producing adipokines as leptin that bridge metabolism and the immune system. Pre-B-cell leukemia homeobox (Pbx)-regulating protein-1 (PREP1) is a ubiquitous homeodomain transcription factor involved in the adipogenic differentiation and insulin-sensitivity processes. Leptin, as pleiotropic adipokine, and TGF-β, known to be expressed by primary pre-adipocytes [adipose-derived stem cells (ASCs)] and mature differentiated adipocytes, modulate inflammatory responses. We aimed to assess for the first time if leptin and TGF-β interfere with PREP1 expression in both ASCs and mature differentiated adi…

Hypoallergenic fragment of Par j 2 increases functional expression of Toll-like receptors in atopic children.

Background: Parietaria judaica (Par j) is one of the main causes of allergy in the Mediterranean countries. The activation of Toll-like receptor 4 (TLR4) by lipopolysaccharide (LPS) inhibits nasal inflammation of atopic children. Objective:  To examine, in vivo and in vitro, the effect of recombinant Par j 2 (rPar j 2) and of its fragments (1–55 and 52–102) on atopic children. Methods:  We used skin prick test for in vivo evaluations. We assessed, in vitro, in peripheral blood mononuclear cells (PBMC), the effect of rPar j 2 and of the two fragments on neutrophil chemotaxis, on CD45RO, on TLR2 and TLR4 expression, on LPS binding and on interferon (IFN)-γ release, by a microchemotaxis chambe…

Cigarette smoke increases BLT2 receptor functions in bronchial epithelial cells: in vitro and ex vivo evidence

Summary Leukotriene B4 (LTB4) is a neutrophil chemotactic molecule with important involvement in the inflammatory responses of chronic obstructive pulmonary disease (COPD). Airway epithelium is emerging as a regulator of innate immune responses to a variety of insults including cigarette smoke, the major risk factor for COPD. In this study we have explored whether cigarette smoke extracts (CSE) or soluble mediators present in distal lung fluid samples (mini-bronchoalveolar lavages) from smokers alter the expression of the LTB4 receptor 2 (BLT2) and peroxisome proliferator-activated receptor-α (PPAR-α) in bronchial epithelial cells. We also evaluated the effects of CSE on the expression of i…

Leptin and leptin receptor expression in asthma.

Background The adipokine leptin is a potential new mediator for bronchial epithelial homeostasis. Asthma is a chronic inflammatory disease characterized by airway remodeling that might affect disease chronicity and severity. TGF-β is a tissue growth factor the dysregulation of which is associated with airway remodeling. Objective We sought to determine whether a bronchial epithelial dysfunction of the leptin/leptin receptor pathway contributes to asthma pathogenesis and severity. Methods We investigated in vitro the presence of leptin/leptin receptor on human bronchial epithelial cells. Then we studied the effect of TGF-β and fluticasone propionate on leptin receptor expression. Finally, th…

Lumican and biglycan expression in lungs of COPD patients

Budesonide increases TLR4 and TLR2 expression in Treg lymphocytes of allergic asthmatics

Abstract Background Reduced innate immunity responses as well as reduced T regulatory activities characterise bronchial asthma. Objectives In this study the effect of budesonide on the expression of TLR4 and TLR2 in T regulatory lymphocyte sub-population was assessed. Methods TLR4 and TLR2 expression in total peripheral blood mononuclear cells (PBMC), in CD4+/CD25+ and in CD4+/CD25− was evaluated, by flow cytometric analysis, in mild intermittent asthmatics (n = 14) and in controls (n = 11). The in vitro effects of budesonide in modulating: TLR4 and TLR2 expression in controls and in asthmatics; IL-10 expression and cytokine release (IL-6 and TNF-α selected by a multiplex assay) in asthmati…

Elastic Fiber Density in Large and Small Airways and Parenchyma in Lungs of Non-Smokers, Smokers and COPD Patients.

Fluticasone furoate maintains epithelial homeostasis via leptin/leptin receptor pathway in nasal cells

Leptin is involved in the lung epithelial homeostasis. Its role in the nasal tract is largely unknown. Allergic rhinitis (AR) is induced by the allergen exposure leading to consequential structural abnormalities in the nasal epithelium. Topical corticosteroids are recommended as first-line therapy in AR. Parietaria pollen is one of the most important allergenic sources in the southern Europe. In vitro, in human nasal epithelial cell line RPMI 2650, we aimed to determine whether allergen stimulation acts on leptin/leptin receptor pathway and how fluticasone furoate (FF) influences this pathway. The effects of the major allergen recombinant Par j 1 (rPar j 1), of FF, of leptin, and of TGF-b1 …

Impairment of leptin/leptin receptor pathway in nasal epithelium from allergic turbinates

BACKGROUND: Allergic rhinitis (AR) is characterized by a remodeling of nasal epithelium. Leptin adipokine has been already identified as a marker of homeostasis in human bronchial epithelial of asthmatics. TGF-β is a multi-functional cytokine and conflicting findings exist regarding its role in the remodeling responses of the upper airways in allergic rhinitis. OBJECTIVE: We sought to investigate ex-vivo the expression of leptin/leptin receptor pathway and TGF-β in human nasal epithelium. METHODS: 41 biopsies of inferior turbinates obtained from allergic patients with AR (A, n = 20) and from healthy control subjects (C, n = 21) were analyzed for leptin/leptin receptor and for TGF-β 1, 2, 3 …

Cellular and Molecular Signatures of Oxidative Stress in Bronchial Epithelial Cell Models Injured by Cigarette Smoke Extract

Exposure of the airways epithelium to environmental insults, including cigarette smoke, results in increased oxidative stress due to unbalance between oxidants and antioxidants in favor of oxidants. Oxidative stress is a feature of inflammation and promotes the progression of chronic lung diseases, including Chronic Obstructive Pulmonary Disease (COPD). Increased oxidative stress leads to exhaustion of antioxidant defenses, alterations in autophagy/mitophagy and cell survival regulatory mechanisms, thus promoting cell senescence. All these events are amplified by the increase of inflammation driven by oxidative stress. Several models of bronchial epithelial cells are used to study the molec…

Notch‐1 signaling activation sustains overexpression of interleukin 33 in the epithelium of nasal polyps

Abstract BACKGROUND: Alterations in the nasal epithelial barrier homeostasis and increased interleukin 33 (IL-33) expression contribute to the pathogenesis of chronic rhinosinusitis with nasal polyps (CRSwNP). AIMS: As Notch-1 signaling is crucial in repair processes of mucosa, the current study assessed Notch-1/Jagged-1 signaling and IL-33 in the epithelium of nasal polyps biopsies from allergic (A-CRSwNP; n = 9) and not allergic (NA-CRSwNP; n = 9) subjects by immunohistochemistry. We also assessed, in a model of nasal epithelial cells, the effects of stimulation of Notch-1 with Jagged-1 on the expression of IL-33 (by flow cytometry, immunofluorescence, and immunocytochemistry), Jagged-1 (…

Extracellular matrix composition in COPD

Extracellular matrix (ECM) composition has an important role in determining airway structure. We postulated that ECM lung composition of chronic obstructive pulmonary disease (COPD) patients differs from that observed in smoking and nonsmoking subjects without airflow obstruction. We determined the fractional areas of elastic fibres, type-I, -III and -IV collagen, versican, decorin, biglycan, lumican, fibronectin and tenascin in different compartments of the large and small airways and lung parenchyma in 26 COPD patients, 26 smokers without COPD and 16 nonsmoking control subjects. The fractional area of elastic fibres was higher in non-obstructed smokers than in COPD and nonsmoking controls…

Oxidative stress and innate immunity responses in cigarette smoke stimulated nasal epithelial cells

Cigarette smoke extracts (CSE) may play a significant role in diseases of the upper airway including chronic rhinosinusitis. Even short term exposure of cigarette smoke has adverse effects on mitochondrial functions and redox homeostasis in tissues which may progress to further complications associated with chronic smoking. Cigarette smoke alters toll-like receptor 4 (TLR4) expression and activation in bronchial epithelial cells. Carbocysteine is an anti-oxidant and mucolytic agent. The effects of carbocysteine on CSE induced oxidative stress and on associated innate immune and inflammatory responses in nasal epithelial cells are largely unknown. The present study was aimed to assess in CSE…

Apigenin affects leptin/leptin receptor pathway and induces cell apoptosis in lung adenocarcinoma cell line

Abstract Background Apigenin, a common edible plant flavonoid, is a well characterised antioxidant. The adipokine leptin exerts proliferative and anti-apoptotic activities in a variety of cell types. In cancer cells, apigenin may induce a pro-apoptotic pathway whereas leptin has an anti-apoptotic role. The purpose of the study is to investigate the role of apigenin and of leptin/leptin receptor pathway on proliferation and on apoptosis in lung adenocarcinoma. Methods Immunocytochemistry, flow cytometry and RT-q-RT PCR, were used to investigate the expression and modulation of leptin receptors on the lung adenocarcinoma cell line A549 in presence or absence of apigenin and of leptin, alone o…

Increased leptin/leptin receptor pathway affects systemic and airway inflammation in COPD former smokers

Andreina Bruno1, Marinella Alessi2, Simona Soresi2, Anna Bonanno1, Loredana Riccobono1, Angela Marina Montalbano1, Giusy Daniela Albano1, Mark Gjomarkaj1, Mirella Profita11Institute of Biomedicine and Molecular Immunology, Italian National Research Council, Palermo, Italy; 2Dipartimento Biomedico di Biomedicina Interna e Specialistica, University Palermo, ItalyBackground: Leptin, a hormone produced mainly by adipose tissue, regulates food intake and energy expenditure. It is involved in inflammatory diseases such as chronic obstructive pulmonary disease (COPD) and its deficiency is associated with increased susceptibility to the infection. The leptin receptor is expressed in the lung and in…

In vitro effects of flunisolide on MMP-9, TIMP-1, fibronectin, TGF-beta1 release and apoptosis in sputum cells freshly isolated from mild to moderate asthmatics

Corticosteroids play an important role in inflammation and remodelling of airways and are considered an important therapeutic target in asthma. Inflammation in asthma is characterized by a dysregulation of eosinophil apoptosis and of markers of airways remodelling. We evaluated the ability of flunisolide to inhibit in vitro the release of metalloproteinases-9 (MMP-9), tissue inhibitor metalloproteinases-1 (TIMP-1), transforming growth factor (TGF-beta) and fibronectin by sputum cells (SC) as well as to induce sputum eosinophil apoptosis.The SC, isolated from induced sputum samples of 12 mild-to-moderate asthmatics, were cultured for 24 h in the presence or absence of flunisolide (1, 10 and …

Association between reduced bronchodilatory effect of deep inspiration and loss of alveolar attachments.

Abstract Background We have previously shown that the bronchodilatory effect of deep inspiration is attenuated in individuals with COPD. This study was designed to investigate whether the impairment in this effect is associated with loss of alveolar attachments. Methods We measured deep inspiration (DI)-induced bronchodilation in 15 individuals with and without COPD (67 ± 2.2 yrs of age, mean ± SEM) undergoing lobar resection for peripheral pulmonary nodule. Prior to surgery, we measured TLCO and determined the bronchodilatory effect of deep inspiration after constricting the airways with methacholine. The number of destroyed alveolar attachments, as well as airway wall area and airway smoo…

Glycoproteins In Large And Small Airways And In Lung Parenchyma Of COPD Patients

Reduced apoptosis of CD8+ T-Lymphocytes in the airways of smokers with mild/moderate COPD

SummaryChronic obstructive pulmonary disease (COPD) is characterised by chronic inflammation in airways and lung parenchyma. CD8+ T-lymphocytes, crucial effector and regulatory cells in inflammation, are increased in the central and peripheral airways in COPD. The aim of this study was to assess the role of apoptosis in the accumulation of CD8+ T-lymphocytes within the airway wall in COPD. We examined the submucosa of transverse sections of central and peripheral airways from post-operative tissues from non-smokers (n = 16), smokers with normal lung function (n = 16), smokers with mild/moderate COPD (n = 16), and smokers with severe/very severe COPD (n = 9). TUNEL and immunohistochemistry t…

FERULIC ACID INHIBITS OXIDATE STRESS AND CELL DEATH INDUCED BY Ab OLIGOMERS: IMPROVED DELIVERY BY SOLID LIPID NANOPARTICLES.

Oxidative stress and dysfunctional mitochondria are among the earliest events in AD, triggering neurodegeneration. The use of natural antioxidants could be a neuroprotective strategy for blocking cell death. Here, the antioxidant action of ferulic acid (FA) on different paths leading to degeneration of recombinant beta-amyloid peptide (rAbeta42) treated cells was investigated. Further, to improve its delivery, a novel drug delivery system (DDS) was used. Solid lipid nanoparticles (SLNs), empty or containing ferulic acid (FA-SNL), were developed as DDS. The resulting particles had small colloidal size and highly negative surface charge in water. Using neuroblastoma cells and rAbeta42 oligome…

Cigarette smoke extract activates human bronchial epithelial cells affecting non-neuronal cholinergic system signalling in vitro.

Abstract Aims Acetylcholine (ACh) is synthesized by Choline Acetyl-Transferase (ChAT) that exerts its physiological effects in airway epithelial cells via muscarinic receptor (MR) activation. We evaluate the effect of ACh stimulation on human bronchial epithelial cells (16-HBE) and test whether cigarette smoke extract (CSE) can modify the basal cellular response to ACh affecting the non-neuronal cholinergic system signalling. Main methods ACh stimulated 16-HBE were tested for ACh-binding, Leukotriene B 4 (LTB 4 ) release and ERK1/2 and NFkB pathway activation. Additionally, we investigated all the aforementioned parameters as well as ChAT and MR proteins and mRNA expression and endogenous A…

An elevated body mass index increases lung volume but reduces airflow in italian schoolchildren

Background Asthma and obesity are important and growing health issues worldwide. Obesity is considered a risk factor for asthma, due to the induction of changes in airway mechanics and altered airway inflammation. Methods We cross-sectionally investigated the effect of increased weight on pulmonary function in a large population sample of healthy children, aged 10–17 yrs living in Palermo, Italy. Explanatory effect of weight on lung function variables were evaluated by multiple linear regression models, taking into account height, gender, and age-class. Results Among the 2,393 subjects, FVC and FEV1 were positively correlated to weight. Multiple regression models showed that the weight beta…

Ceftaroline modulates the innate immune and host defense responses of immunocompetent cells exposed to cigarette smoke.

Abstract Background Cigarette smoke, the principal risk factor for chronic obstructive pulmonary disease (COPD), negatively influences the effectiveness of the immune system’s response to a pathogen. The antibiotic ceftaroline exerts immune-modulatory effects in bronchial epithelial cells exposed to cigarette smoke. Aims and methods The present study aims to assess the effects of ceftaroline on TLR2 and TLR4 expression, LPS binding and TNF-α and human beta defensin (HBD2) release in an undifferentiated and PMA-differentiated human monocyte cell line (THP-1) exposed or not to cigarette smoke extracts (CSE). TLR2, TLR4, and LPS binding were assessed by flow cytometry, TNF-α and HBD2 release w…

DOES LEPTIN PLAY A CYTOKINE-LIKE ROLE WITHIN THE AIRWAYS OF COPD PATIENTS?

The leptin-leptin receptor system might be up-regulated in the airways of chronic obstructive pulmonary disease (COPD). In bronchial biopsies obtained from normal subjects and smokers, with and without COPD, the present study examined leptin and leptin-receptor expression and their co-localisation in airway and inflammatory cells. Combining immunohistochemistry with terminal deoxynucleotidyl transferase dUTP nick end-labelling techniques, apoptosis in airway and inflammatory cells and in leptin and leptin-receptor expressing cells was investigated. In the epithelial cells both leptin and leptin-receptor expression was higher in normal subjects than in smokers and COPD subjects. By contrast,…

TLR4 upregulation underpins airway neutrophilia in smokers with chronic obstructive pulmonary disease and acute respiratory failure

Activation of Toll-like receptors (TLR) seems to be involved in the pathogenesis of chronic obstructive pulmonary disease (COPD). Upon TLR activation the release of defensins, including human beta defensin 2 (HBD-2), may occur. In this study, we explored the innate responses in patients with respiratory failure, with and without COPD, requiring intubation and mechanical ventilation. Mini-bronchoalveolar lavage (mini-BAL) samples were collected from nonsmoker subjects without COPD (n = 10), smokers without COPD (n = 6), and smokers with COPD (n = 15). TLR4, TLR2, and HBD-2 expression was evaluated by immunocytochemistry; interleukin (IL)-8, IP-10, and HBD-2 concentrations were evaluated by e…

Carbocysteine counteracts the effects of cigarette smoke on cell growth and on the SIRT1/FoxO3 axis in bronchial epithelial cells

Abstract Background Cigarette smoke may accelerate cellular senescence by increasing oxidative stress. Altered proliferation and altered expression of anti-aging factors, including SIRT1 and FoxO3, characterise cellular senescence. The effects of carbocysteine on the SIRT1/FoxO3 axis and on downstream molecular mechanisms in human bronchial epithelial cells exposed to cigarette smoke are largely unknown. Aims Aim of this study was to explore whether carbocysteine modulated SIRT1/FoxO3 axis, and downstream molecular mechanisms associated to cellular senescence, in a bronchial epithelial cell line (16-HBE) exposed to cigarette smoke. Methods 16HBE cells were stimulated with/without cigarette …

A New Academic Quality at Work Tool (AQ@workT) to Assess the Quality of Life at Work in the Italian Academic Context

Refereed/Peer-reviewed The present study provides evidence for a valid and reliable tool, the Academic Quality at Work Tool (AQ@workT), to investigate the quality of life at work in academics within the Italian university sector. The AQ@workT was developed by the QoL@Work research team, namely a group of expert academics in the field of work and organizational psychology affiliated with the Italian Association of Psychologists. The tool is grounded in the job demands-resources model and its psychometric properties were assessed in three studies comprising a wide sample of lecturers, researchers, and professors: a pilot study (N = 120), a calibration study (N = 1084), and a validation study …

Remodeling of bronchial and pulmonary muscular arteries in mild/moderate COPD

Pulmonary hypertension is well documented in severe COPD but little is known about vascular remodeling in mild/moderate patients. Aim:To investigate bronchial and pulmonary muscular arteries morphology and the expression of elastic fibers (EF) and collagen I in the lungs of mild/moderate COPD patients. Methods:Lung tissue of 18 COPD subject (FEV1:67±15%pred), 14 non-obstructed smokers(NOS) (FEV1:95±10%pred) and 11 never-smoking controls(CTRL) (FEV1:108±15%pred) was used to analyze the morphology of bronchial and pulmonary muscular arteries and the expression of EF and collagen I in the tunica intima, media and adventitia, using immune- and histochemistry and image analysis. Values (mean±SD)…