Plasma leptin and vascular endothelial growth factor (VEGF) in normal subjects at high altitude (5050 m)

Context: High altitude (HA) is a model of severe hypoxia exposure in humans. We hypothesized that nocturnal hypoxemia or acute maximal exercise at HA might affect plasma leptin and VEGF levels. Objectives: Plasma leptin, VEGF and other metabolic variables were studied after nocturnal pulse oximetry and after maximal exercise in healthy lowlanders on the 3rd-4th day of stay in Lobuche (5050 m, HA) and after return to sea level (SL). Results: Leptin was similar at SL or HA in both pre- and post-exercise conditions. Pre-exercise VEGF at HA was lower, and cortisol was higher, than at SL, suggesting that nocturnal intermittent hypoxia associated with periodic breathing at HA might affect these v…

Reduced airway responsiveness in non elite runners

Med Sci Sports Exerc. 2005 Dec;37(12):2019-25. Reduced airway responsiveness in nonelite runners. Scichilone N, Morici G, Marchese R, Bonanno A, Profita M, Togias A, Bonsignore MR. SourceInstitute of Medicine and Pneumology, Respiratory Unit; University of Palermo, Italy. n.scichilone@libero.it Abstract PURPOSE: The effects of endurance training on airway responsiveness in nonasthmatic subjects are poorly defined. We hypothesized that airway responsiveness may differ between none-lite endurance athletes and sedentary subjects, and studied healthy, nonelite runners and sedentary controls by single-dose methacholine challenges carried out in the absence of deep inspirations, in that deep insp…

Similar cellular composition of induced sputum in Marathon and Half-Marathon runners

In our previous studies, we reported increased neutrophil (PMN) differential counts in induced sputum of marathon (M) runners (Bonsignore et al, 2001). Conversely, increased bronchial epithelial cell (BEC) differential counts were found in half-marathon (HM) runners (Chimenti et al, 2010). To better understand the differences previously found between M and HM runners, we studied 11 non-asthmatic amateur athletes (HM n=6, M n=5, age: 44.5±6.7 yrs, race time: HM 101±18 min, M 218±35 min) participating to the 2012 Palermo Marathon. We collected induced sputum samples 4 to 5 days before the race (PRE), 2 hours after the race (RACE), and the following morning (POST). Induced sputum was processed…

Airway cell composition at rest and after an all-out test in competitive rowers

Med Sci Sports Exerc. 2004 Oct;36(10):1723-9. Airway cell composition at rest and after an all-out test in competitive rowers. Morici G, Bonsignore MR, Zangla D, Riccobono L, Profita M, Bonanno A, Paternò A, Di Giorgi R, Mirabella F, Chimenti L, Benigno A, Vignola AM, Bellia V, Amato G, Bonsignore G. SourceDepartment of Experimental Medicine Italian National Research Council (CNR), Palermo, Italy. Abstract PURPOSES: This study was designed to assess: a) whether rowing affects airway cell composition, and b) the possible relationship between the degree of ventilation during exercise and airway cells. SUBJECTS AND METHODS: In nine young, nonasthmatic competitive rowers (mean age +/- SD: 16.2 …

Endurance training damages small airway epithelium in mice.

RATIONALE: In athletes, airway inflammatory cells were found to be increased in induced sputum or bronchial biopsies. Most data were obtained after exposure to cold and dry air at rest or during exercise. Whether training affects epithelial and inflammatory cells in small airways is unknown. OBJECTIVES: To test whether endurance training under standard environmental conditions causes epithelial damage and inflammation in the small airways of mice. METHODS AND MEASUREMENTS: Formalin-fixed, paraffin-embedded lung sections were obtained in sedentary (n = 14) and endurance-trained (n = 16) Swiss mice at baseline and after 15, 30, and 45 days of training. The following variables were assessed (m…

Increased airway inflammatory cells in endurance athletes: what do they mean?

Background Inflammatory cells are increased in the airways of end urance athletes, but their role in causing exercise-induced respiratory symptoms and bronchoconstriction, or their possible long-term consequences, are uncertain. Aim To put the results of athlete studies in perspective, by analysing the pathogenesis of airway cell changes and their impact on respiratory function. Results Athletes of different endurance sports at rest showed increased airway neutrophils. Elite swimmers and skiers also showed large increases in airway eosinophils and lymphocytes, possibly related to chronic, exercise-related exposure to irritants or cold and dry air, respectively. Post-exercise studies reporte…

Chronic obstructive pulmonary disease and neutrophil infiltration: role of cigarette smoke and cyclooxygenase products.

Cigarette smoke is the main cause of chronic obstructive pulmonary disease (COPD), where it can contribute to the observed airway inflammation. PGE(2) is produced within human airways, and both pro- and anti-inflammatory activities have been reported. We quantitated PGE(2) concentrations in induced sputum supernatants from different groups of subjects and correlated the obtained values to neutrophil infiltration as well as to the expression of cyclooxygenase-2 (COX-2). Cigarette smoke extract (CSE) was used to evaluate the effect of smoking on COX-2 and PGE(2) receptor expression as well as on PGE(2) release in neutrophils and alveolar macrophages (AM) obtained from normal donors. The effec…

Biomarkers of Oxidative Stress in the Upper and Lower Airways of Atopic Children.

Airway inflammation in nonasthmatic amateur runners

Elite athletes show a high prevalence of symptoms and signs of asthma, but no study has assessed the acute effects of endurance exercise on airway cells in nonasthmatic athletes. We measured exhaled nitric oxide (NO) and collected samples of induced sputum after 3% NaCl aerosol administration for 20 min in nonasthmatic middle-aged amateur runners after the Fourth Palermo International Marathon and 6–9 wk later (habitual training period) at baseline. After the marathon, exhaled NO ( n = 9 subjects) was higher [27 ± 9 parts/billion (ppb)] than at baseline (12 ± 4 ppb; P < 0.0005). Polymorphonuclear neutrophil (PMN) counts in induced sputum were much higher in runners (91.2 ± 3.6% of total…

Supramaximal exercise mobilizes hematopoietic progenitors and reticulocytes in athletes

Am J Physiol Regul Integr Comp Physiol. 2005 Nov;289(5):R1496-503. Epub 2005 Jul 14. Supramaximal exercise mobilizes hematopoietic progenitors and reticulocytes in athletes. Morici G, Zangla D, Santoro A, Pelosi E, Petrucci E, Gioia M, Bonanno A, Profita M, Bellia V, Testa U, Bonsignore MR. SourceDepartment of Experimental Medicine, University of Palermo, Italy. Abstract Marathon runners show increased circulating CD34+ cell counts and postexercise release of interleukin-6 (IL-6), granulocyte-colony stimulating factor (G-CSF) and flt3-ligand (Bonsignore MR, Morici G, Santoro A, Pegano M, Cascio L, Bonnano A, Abate P, Mirabella F, Profita M, Insalaco G, Gioia M, Vignola AM, Majolino I, Testa…

Circulating hematopoietic progenitor cells in runners

Because endurance exercise causes release of mediators and growth factors active on the bone marrow, we asked whether it might affect circulating hematopoietic progenitor cells (HPCs) in amateur runners [ n = 16, age: 41.8 ± 13.5 (SD) yr, training: 93.8 ± 31.8 km/wk] compared with sedentary controls ( n = 9, age: 39.4 ± 10.2 yr). HPCs, plasma cortisol, interleukin (IL)-6, granulocyte colony-stimulating factor (G-CSF), and the growth factor fms-like tyrosine kinase-3 (flt3)-ligand were measured at rest and after a marathon (M; n = 8) or half-marathon (HM; n = 8). Circulating HPC counts (i.e., CD34+cells and their subpopulations) were three- to fourfold higher in runners than in controls at b…

Hemopoietic and angiogenetic progenitors in healthy athletes: different responses to endurance and maximal exercise

J Appl Physiol. 2010 Jul;109(1):60-7. Epub 2010 May 6. Hemopoietic and angiogenetic progenitors in healthy athletes: different responses to endurance and maximal exercise. Bonsignore MR, Morici G, Riccioni R, Huertas A, Petrucci E, Veca M, Mariani G, Bonanno A, Chimenti L, Gioia M, Palange P, Testa U. SourceBiomedical Department, Internal and Specialistic Medicine (DIBIMIS), Section of Pneumology, University of Palermo, Via Trabucco, 180, 90146 Palermo, Italy. marisa@ibim.cnr.it Abstract The effects of endurance or maximal exercise on mobilization of bone marrow-derived hemopoietic and angiogenetic progenitors in healthy subjects are poorly defined. In 10 healthy amateur runners, we collect…

Increased prostaglandin E2 concentrations and cyclooxygenase-2 expression in asthmatic subjects with sputum eosinophilia.

Abstract Background Prostaglandin E 2 (PGE 2 ) is known to be produced within human airways, but it is not clear whether in airway diseases it can play a deleterious or a beneficial role. Recently it has been reported that PGE 2 can enhance eosinophil survival in vitro. Objective To evaluate whether the concentrations of PGE 2 in asthmatic airways correlate with the number of eosinophils and can be responsible for eosinophil-enhanced survival and to identify the cyclooxygenase isoform contributing to the synthesis of PGE 2 by cells present in asthmatic airways. Methods Reversed-phase high-performance liquid chromatography and/or specific radioimmunoassay was used to measure PGE 2 concentrat…

Acetylcholine leads to signal transducer and activator of transcription 1 (STAT-1) mediated oxidative/nitrosative stress in human bronchial epithelial cell line

AbstractThe induction of nitric oxide synthase (iNOS) expression via the signal transducer and activator of transcription 1 (STAT-1) is involved in the mechanism of oxidative/nitrosative stress. We investigated whether acetylcholine (ACh) generates oxidative/nitrosative stress in bronchial epithelial cells during airway inflammation of COPD and evaluated the effects of Tiotropium, a once-daily antimuscarinic drug, and Olodaterol, a long-acting β2-agonist on these mechanisms. Human bronchial epithelial cells (16-HBE) were stimulated (4h, 37°C) with induced sputum supernatants (ISSs) from healthy controls (HC) (n=10), healthy smokers (HS) (n=10) or COPD patients (n=10), as well as with ACh (f…

Reticulocytes in untreated obstructive sleep apnoea.

Background and Aim. The short, repetitive hypoxaemic episodes observed in obstructive sleep apnoea (OSA) may determine small augmentations in mature red blood cells. It is unknown whether they affect reticulocyte release. This study explored whether the number and degree of maturation of circulating reticulocytes may be altered in OSA, possibly through the effect of erythropoietin. Methods. Fifty male adult patients with suspected OSA, normoxic during wakefulness, were studied. After nocturnal polysomnography, a blood sample was withdrawn for blood cells count, erythropoietin, iron and transferrin determination. Reticulocyte concentration and degree of immaturity [high (H), medium (M), or l…

Environmental conditions, air pollutants, and airway cells in runners: a longitudinal field study

Runners have increased numbers of neutrophils in the airways at rest and after exercise compared with sedentary individuals. The aim of this study was to determine whether Mediterranean seasonal changes in temperature, humidity or airborne pollutants affect the airway cells of runners training outdoors in an urban environment. In nine male amateur runners, cell composition, apoptosis, and inflammatory mediators were measured in induced sputum collected at rest (baseline) and the morning after races held in the fall (21 km), winter (12 km), and summer (10 km). Concentrations of air pollutants were below the alert threshold at all times. Neutrophil differential counts tended to increase after…

Increased Levels of Elastase and α1-Antitrypsin in Sputum of Asthmatic Patients

Asthma and chronic bronchitis are inflammatory diseases associated with remodeling of the extracellular matrix (ECM). Elastin, a major component of the ECM in the airways, has been previously found to be disrupted in asthma and chronic bronchitis. This study was aimed at evaluating whether elastin disruption might be associated with an imbalance between elastase (active and total) and alpha1-proteinase inhibitor (alpha1-PI), the main inhibitor of elastase. We measured elastase and alpha1-PI in induced sputum obtained from 16 control subjects, 10 healthy smokers, 19 asthmatic patients, and 10 chronic bronchitis patients. We also assessed the possible origin of elastase, evaluating its levels…

Effect of age and asthma duration upon elastase and alpha1-antitrypsin levels in adult asthmatics

In asthmatic subjects an imbalance between elastase and alpha1-antitrypsin (alpha1-PI) exists. This study aims to evaluate whether ageing per se affects the levels of elastase. Both young and elderly asthmatics with comparable severity and duration of disease, as well as young and elderly healthy subjects, underwent an induced sputum procedure to measure levels of elastase and alpha1-PI. The percentage of sputum neutrophils and eosinophils was higher in young and elderly asthmatics than in young and elderly controls. The levels of both total and active elastase were significantly higher in young and elderly asthmatics than in young and elderly controls, and directly correlated with the perc…

Novel Perspectives in the Detection of Oral and Nasal Oxidative Stress and Inflammation in Pediatric United Airway Diseases

United airway disease (UAD) concept proposed that asthma and rhinitis are both different clinical manifestation of a single inflammatory process. The aim of this study is to assess in upper and lower airways the level of inflammation and oxidative stress and to investigate the relationship between biomarkers in persistent allergic rhinitis (PER) and in concomitant asthma with PER. By a crosssectional study we measured oral and nasal (FENO) and oral and nasal EBC 8-isoprostane, LTB4 and PGE2 in children with PER (n=14) and with PER and concomitant intermittent asthma (IA; n=25), mild persistent asthma (mA; n=28), moderate persistent asthma (MA; n=13) and in Healthy Controls (HCs; n=13). Oral…

IκB kinase-driven nuclear factor-κB activation in patients with asthma and chronic obstructive pulmonary disease.

Background Nuclear factor-κB (NF-κB) is a transcriptional factor of different inflammatory patterns involved in asthma and chronic obstructive pulmonary disease (COPD) that is tightly controlled by IκB kinase (IKK) complex. Objective We investigated the dysregulation of IKK-driven NF-κB activation in patients with asthma and COPD. Methods We assessed IKKα and IKKβ expression and activation, their regulation by glucocorticosteroids, and their involvement in IL-8 synthesis in PBMCs isolated from asthmatic patients, healthy smokers (HSs), patients with COPD, and control subjects. PBMCs from control subjects were stimulated with TNF-α and cigarette smoke extract in the presence or absence of fl…

Variable Release of Interleukin-8 after Hyperosmolar Exposure of Bronchial Epithelial Cell Lines.

Effect of nebulized beclomethasone on airway inflammation and clinical status of children with allergic asthma and rhinitis: a randomized, double-blind, placebo-controlled study.

We aimed to evaluate the therapeutic effect of nebulized beclomethasone dipropionate (nBDP) on both allergic asthma and rhinitis. In a randomized, double-blind, placebo-controlled study, 40 children (mean age 10.7 ± 2.1 years) with allergic asthma and rhinitis received either nBDP (daily dose of 800 µg, administered twice daily) or placebo for 4 weeks (with a face mask), after a 2-week run-in period of clinical assessment. Nasal and oral fractional exhaled nitric oxide (FeNO) measurements together with pulmonary function tests, nasal and oral exhaled breath condensate (EBC) collection for pH and interleukin-5 (IL-5) measurements as well as nasal and bronchial symptom scores were obtained at…

Nebulized Beclomethasone In The Treatment Of Childhood Mild Intermittent Asthma With Seasonal Allergic Rhinitis. A Randomized, Double-Blind, Placebo-Controlled Study

Urinary leukotriene E4 in the assessment of nocturnal asthma

Urinary leukotriene E4 (LTE4) is a marker of the body's production of cysteinyl LTs, important mediators of airway inflammation. The role of the latter in nocturnal asthma is a topic of increasing interest.This investigation was aimed at determining whether nighttime attacks are associated with increased release of LTs, expressed by urinary LTE4, and the relationship between the two phenomena.Three groups were studied: group A, seven control subjects; group B, nine asthmatic patients without nocturnal attacks; and group C, nine asthmatic patients with a comparable daytime FEV1 but who were experiencing nocturnal exacerbations (morning dips in peak expiratory flow greater than 20%). Urine wa…

β2 long-acting and anticholinergic drugs control TGF-β1-mediated neutrophilic inflammation in COPD

AbstractWe quantified TGF-β1 and acetylcholine (ACh) concentrations in induced sputum supernatants (ISSs) from 18 healthy controls (HC), 22 healthy smokers (HS) and 21 COPDs. ISSs from HC, HS and COPD as well as rhTGF-β1 were also tested in neutrophil adhesion and in mAChR2, mAChR3 and ChAT expression experiments in human bronchial epithelial cells (16-HBE). Finally, we evaluated the effects of Olodaterol (a novel inhaled β2-adrenoceptor agonist) and Tiotropium Spiriva®, alone or in combination, on neutrophil adhesion and mAChRs and ChAT expression in stimulated 16-HBE. The results showed that 1) TGF-β1 and ACh concentrations are increased in ISSs from COPD in comparison to HC and HS, and T…

Increased levels of Th17 cells are associated with non-neuronal acetylcholine in COPD patients.

T-lymphocytes, including Th17-cells and T-cells expressing acetylcholine (ACh), are key components of systemic inflammation in chronic obstructive pulmonary disease (COPD). We investigated whether ACh promotes Th17 cells in COPD. ACh, IL-17A, IL-22, RORγt, FOXP3 expression and AChIL-17A, AChIL-22, AChRORγt coexpression was evaluated in peripheral blood mononuclear cells (PBMC) from COPD patients (n=16), healthy smokers (HS) (n=12) and healthy control subjects (HC) (n=13) (cultured for 48 h with PMA) by flow cytometry. Furthermore, we studied the effect of Tiotropium (Spiriva®) (100 nM) and Olodaterol (1nM) alone or in combination, and of hemicholinium-3 (50 μM) on AChIL-17A, AChIL-22, AChRO…

Acetylcholine mediates the release of IL-8 in human bronchial epithelial cells by a NFkB/ERK-dependent mechanism

Acetylcholine may play a role in cell activation and airway inflammation. We evaluated the levels of both mRNA and protein of muscarinic M(1), M(2), M(3) receptors in human bronchial epithelial cell line (16HBE). 16HBE cells were also stimulated with acetylcholine and extracellular signal-regulated kinase1/2 (ERK1/2) and NFkB pathway activation as well as the IL-8 release was assessed in the presence or absence of the inhibitor of Protein-kinase (PKC) (GF109203X), of the inhibitor of mitogenic activated protein-kinase kinase (MAPKK) (PDO9805), of the inhibitor of kinaseB-alpha phosphorilation (pIkBalpha) (BAY11-7082), and of muscarinic receptor antagonists tiotropium bromide, 4-Diphenylacet…

“Cysteinyl leukotriene-1 receptor activation in a human bronchial epithelial cell line leads to signal transducer and activator of transcription 1-mediated eosinophil adhesion.”

Abstract We studied the effect of leukotriene D(4) (LTD(4)) on a human bronchial epithelial cell line (16HBE) overexpressing the cysteinyl leukotriene (CysLT) (1) receptor (HBECysLT(1)R), looking at the associated signal transduction mechanisms as well as at effects on inflammatory cell adhesion. The results obtained showed that LTD(4) increases the phosphorylation of extracellular signal-regulated protein kinase (ERK) 1/2 and of the signal transducer and activator of transcription 1 (STAT-1) in serine 727 (STAT-1Ser727), resulting in increased eosinophil adhesion to HBECysLT(1)R, associated with enhanced surface expression of intercellular adhesion molecule (ICAM) 1. Pretreatment with a Cy…

15-Lipoxygenase expression and 15(S)-hydroxyeicoisatetraenoic acid release and reincorporation in induced sputum of asthmatic subjects

Recent evidence shows that 15(S)-hydroxy-eicoisatetraenoic acid (15[S]-HETE) can be released and rapidly reincorporated into cellular lipids. These mechanisms exert several immunoregulatory functions that may be relevant in airway inflammation.Our purpose was to evaluate the levels of both soluble and cell-associated 15(S)-HETE and to examine 15-lipoxygenase (15-LO) messenger RNA (mRNA) expression in sputum samples obtained from 10 control and 18 asthmatic subjects.Levels of 15(S)-HETE were measured by reverse-phase HPLC separation followed by RIA in supernatants and in cell membrane-extracted phospholipids after acid hydrolysis. 15-LO mRNA was evaluated by primed in situ hybridization (PRI…

Noninvasive methods for the detection of upper and lower airway inflammation in atopic children

Background Exhaled nitric oxide (FE NO ) and exhaled breath condensate (EBC) are noninvasive methods to assess inflammation. Objective To investigate the role of the FE NO and of the EBC pH and IL-5 levels in atopic children. Methods We evaluated oral and nasal FE NO and the pH and IL-5 of oral and nasal EBC in children with atopic dermatitis (AD; n=18), allergic rhinitis (AR; n=18), intermittent asthma (n = 21), moderate persistent asthma (n = 18), and healthy controls (HCs; n=16). Results Oral FE NO was significantly increased in asthma, whereas the nasal values were increased in AR and asthma in comparison with HCs. The pH of oral EBC was lower in AD and asthma than in AR and HCs, wherea…

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 …

IL-17A induces chromatin remodeling promoting IL-8 release in bronchial epithelial cells: Effect of Tiotropium

Abstract Aims IL-17A plays a key role in the persistence of airway inflammation, oxidative stress, and reduction of steroid-sensitivity in COPD. We studied the effect of IL-17A on chromatin remodeling and IL-8 production. Main methods We measured the levels of IL-8 and IL-17A in induced sputum supernatants (ISS) from healthy controls (HCs), healthy smokers (HSs), and COPD patients by enzyme-linked immunosorbent assay (ELISA). A human bronchial epithelial cell line (16HBE) was stimulated with ISS from HCs, HSs, or COPD subjects. IL-8 was evaluated in 16HBE by Western blot and real-time polymerase chain reaction (PCR). Histone deacetylase 2 (HDAC2), acetyl histone H3 (Ac-His H3) (k9) and inhi…

Th17 immunity in children with allergic asthma and rhinitis: a pharmacological approach

Th17 cells and IL-17A play a role in the development and progression of allergic diseases. We analyzed the IL-17A levels in sputum supernatants (Ss), nasal wash (NW) and plasma (P) from Healthy Controls (HC) and children with Asthma/Rhinitis. We tested the expression of IL-17A, RORγ(t) and FOXP3 in peripheral blood T-lymphocytes from intermittent and mild-moderate asthma. The effect of Budesonide and Formoterol was tested "in vitro" on IL-17A, RORγ(t) and FOXP3 expression in cultured T-lymphocytes from mild-moderate asthma/persistent rhinitis patients, and on nasal and bronchial epithelial cells stimulated with NW and Ss from mild-moderate asthma/persistent rhinitis. Further, the effect of …

Airway cells after swimming outdoors or in the sea in nonasthmatic athletes

BONSIGNORE, M. R., G. MORICI, L. RICCOBONO, M. PROFITA, A. BONANNO, A. PATERNO, R. DI GIORGI, L. CHIMENTI, P. ABATE, F. MIRABELLA, A. M. VIGNOLA, and G. BONSIGNORE. Airway Cells after Swimming Outdoors or in the Sea in Nonasthmatic Athletes. Med. Sci. Sports Exerc., Vol. 35, No. 7, pp. 1146–1152, 2003. Marathon runners and elite swimmers showed increased inflammatory cells in the airways at baseline. Although airway neutrophils increase further after a marathon race, the airway response to swimming is unknown. The aim of this study was to assess the effects of swimming on airway cells. To avoid the concomitant effects of chronic exposure to chlorine, the study was conducted in seven nonasth…

The Role of Transforming Growth Factor-β1 in Airway Inflammation of Childhood Asthma

TGF-beta-targeting structural and inflammatory cells has been implicated in the mechanisms leading to the inflammatory and restructuring processes in asthma, suggesting an impact of TGF-beta1 signaling on the development and persistency of this disease. We investigated the potential early involvement of TGF-beta1 activity in the immunological and molecular mechanisms underlying progression of inflammation in childhood asthma. We evaluated the levels of TGF-beta1 in induced sputum supernatants (ISSs) and the expression of small mother cell against decapentaplegic (Smad) 2 and Smad7 proteins in induced sputum cells (ISCs) from children with intermittent asthma (IA), moderate asthma (MA) and c…

Relaxin in Obstructive Sleep Apnea: Relationship with Blood Pressure and Inflammatory Mediators

<b><i>Background:</i></b> Obstructive sleep apnea (OSA) is associated with nocturnal intermittent hypoxia, which may be responsible for increased circulating levels of vascular endothelial growth factor (VEGF) and inflammatory mediators, such as metalloproteinases (MMPs), and which contributes to the pathogenesis of systemic hypertension. Why some OSA patients remain normotensive is poorly understood. Relaxin-2, a pregnancy hormone, may sometimes circulate in men and could increase in hypoxic conditions. It exerts a vasodilatory activity and can modulate the release of molecules, such as MMPs and VEGF. <b><i>Objectives:</i></b> The objective o…

LTB4 is present in exudative pleural effusions and contributes actively to neutrophil recruitment in the inflamed pleural space

SUMMARY The pleural space is a virtual compartment between the lung and chest wall that becomes filled with fluid and inflammatory cells during a variety of respiratory diseases. Here, we study the potential role of the eicosanoid metabolite leukotriene B4 (LTB4) in disparate diseases leading to acute (pneumonia) or chronic (tuberculosis, cancer) inflammation of the pleural space. LTB4 concentrations were significantly higher in pleural fluid due to pneumonia, tuberculosis and cancer with respect to congestive heart failure and correlated with neutrophil elastase, which is used as an indication of state of activation of neutrophils in the pleural space. Moreover, pleural LTB4 was biological…

Muscarinic receptors, leukotriene B4 production and neutrophilic inflammation in COPD patients.

Background:  Acetylcholine (ACh) plays an important role in smooth muscle contraction and in the development of airway narrowing; preliminary evidences led us to hypothesize that ACh might also play a role in the development of airways inflammation in chronic obstructive pulmonary disease (COPD). Methods:  We evaluated the concentrations of leukotriene B4 (LTB4) in induced sputum, and the expression of Ach M1, M2, and M3 receptors in sputum cells (SC) obtained from 16 patients with COPD, 11 smokers, and 14 control subjects. The SC were also treated with ACh and the production of LTB4 assessed in the presence or absence of a muscarinic antagonist (oxitropium). In blood monocytes, we evaluate…

IL-17A-associated IKK-α signaling induced TSLP production in epithelial cells of COPD patients.

Thymic stromal lymphopoietin (TSLP) is a cytokine expressed in the epithelium, involved in the pathogenesis of chronic disease. IL-17A regulates airway inflammation, oxidative stress, and reduction of steroid sensitivity in chronic obstructive pulmonary disease (COPD). TSLP and IL-17A were measured in induced sputum supernatants (ISs) from healthy controls (HC), healthy smokers (HS), and COPD patients by enzyme-linked immunosorbent assay. Human bronchial epithelial cell line (16HBE) and normal bronchial epithelial cells were stimulated with rhIL-17A or ISs from COPD patients to evaluate TSLP protein and mRNA expression. The effects of the depletion of IL-17A in ISs, an anticholinergic drug,…

In vitro anticholinergic drugs affect CD8+ peripheral blood T-cells apoptosis in COPD

Novel pharmacological strategies are aimed at the resolution of systemic inflammation in COPD potentiating peripheral blood T-cell (PBT-cell) apoptosis. Although muscarinic acetylcholine receptors (mAChRs) M(3) and choline-acetyltransferase (ChAT) participate in the airway inflammation of COPD, their role in PBT-cell apoptosis remains unexplained. We evaluated in PBT-cells from COPD patients, smoker (S) and control (C) subjects: (1) apoptosis (by annexin V binding), (2) mAChR M(3) and ChAT expression, acetylcholine (ACh)-binding; (3) choline levels in serum and PBT-cells extracts. We tested the effects of Tiotropium (Spiriva(®)) and hemicholinium-3 (HCh-3) on apoptosis, NFκB pathway, caspas…

Blood pressure changes after automatic and fixed CPAP in obstructive sleep apnea. Relationship with nocturnal sympathetic activity.

Treatment of obstructive sleep apnea (OSA) by continuous positive airway pressure (CPAP) usually causes a reduction in blood pressure (BP), but several factors may interfere with its effects. In addition, although a high sympathetic activity is considered a major contributor to increased BP in OSA, a relationship between changes in BP and in sympathetic nervous system activity after OSA treatment is uncertain. This study was undertaken to assess if, in OSA subjects under no pharmacologic treatment, treatment by CPAP applied at variable levels by an automatic device (APAP) may be followed by a BP reduction, and if that treatment is associated with parallel changes in BP and catecholamine exc…

Effects of exercise training and montelukast in children with mild asthma

Data from the general population suggest that habitual exercise decreases bronchial responsiveness, but the possible role of exercise in asthmatics is undefined. The leukotriene receptor antagonist montelukast decreases bronchial responsiveness and exercise-induced symptoms in asthmatic children. This randomized study in children with mild asthma evaluated the combined effects of aerobic training for 12 wk and montelukast or placebo on bronchial responsiveness (BHR) to methacholine, exercise-induced bronchoconstriction (EIB), inflammatory markers in exhaled breath condensate (EBC), and asthma exacerbations.Fifty children (mean age +/- SD: 10.2 +/- 2.4 yr) with mild stable asthma were random…

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…

25-Hydroxyvitamin D, IL-31, and IL-33 in Children with Allergic Disease of the Airways

Low vitamin D is involved in allergic asthma and rhinitis. IL-31 and IL-33 correlate with Th2-associated cytokines in allergic disease. We investigated whether low vitamin D is linked with circulating IL-31 and IL-33 in children with allergic disease of the airways. 25-Hydroxyvitamin D [25(OH) Vit D], IL-31, and IL-33 plasma levels were measured in 28 controls (HC), 11 allergic rhinitis (AR) patients, and 35 allergic asthma with rhinitis (AAR) patients. We found significant lower levels of 25(OH) Vit D in AR and in AAR than in HC. IL-31 and IL-33 plasma levels significantly increased in AAR than HC. IL-31 and IL-33 positively correlated in AR and AAR. 25(OH) Vit D deficient AAR had higher l…

Cigarette smoke alters the EZH2/DAB2IP expression in bronchial epithelial cells. A risk factor for lung cancer in COPD patients

Cigarette smoke is an environmental risk factor for COPD and Lung cancer, leading causes of morbidity and mortality worldwide. In cancer, enhancer of zeste homolog 2 (EZH2) silenced disabled homolog 2 interacting protein gene (DAB2IP) (tumor-suppressor gene) bytri-methylation of lysine 27 on histone H3 (H3K27me3). We studied EZH2 and DAB2IP expression in airway epithelial cells from COPD patients and their potential involvement in the progression of COPD toward lung cancer. We assessed EZH2 and DAB2IPimmunoreactivity in bronchial epithelial cells from surgical specimens of COPD patients and healthy control subjects (HC) by immunohistochemistry. Bronchial epithelial cell line (16HBE), primar…

Beclomethasone dipropionate and formoterol reduce oxidative/nitrosative stress generated by cigarette smoke extracts and IL-17A in human bronchial epithelial cells.

Interleukin-17A (IL-17A), cigarette smoke and oxidative/nitrosative stress are involved in inflammatory airway diseases, and the mechanisms behind these processes are still poorly understood. We investigated whether recombinant human IL-17A (rhIL-17A), in combination with cigarette smoke extracts (CSE), increases the levels of inducibile nitric oxide synthase (iNOS), reactive oxygen species, nitrotyrosine (NT) and the activation of signal transducer and activator of transcription 1 (STAT-1) in normal human bronchial epithelial cells (16HBE). The effect of beclomethasone dipropionate (BDP), formoterol and their combination was also evaluated. We demonstrated that rhIL-17A or CSE alone increa…

Bronchial epithelial damage after a half-marathon in nonasthmatic amateur runners.

Am J Physiol Lung Cell Mol Physiol. 2010 Jun;298(6):L857-62. Epub 2010 Apr 2. Bronchial epithelial damage after a half-marathon in nonasthmatic amateur runners. Chimenti L, Morici G, Paternò A, Santagata R, Bonanno A, Profita M, Riccobono L, Bellia V, Bonsignore MR. SourceDept. Biomedico Di Medicina Interna & Specialistica, Section of Pneumology, Univ. of Palermo, Via Trabucco 180, 90146 Palermo, Italy. laurachimenti@yahoo.it Abstract High neutrophil counts in induced sputum have been found in nonasthmatic amateur runners at rest and after a marathon, but the pathogenesis of airway neutrophilia in athletes is still poorly understood. Bronchial epithelial damage may occur during intense exer…

Cigarette smoke alters non-neuronal cholinergic system components inducing MUC5AC production in the H292 cell line.

Abstract Cigarette smoke extract (CSE) affects the expression of Choline Acetyl-Transferase (ChAT), muscarinic acetylcholine receptors, and mucin production in bronchial epithelial cells. Mucin 5AC (MUC5AC), muscarinic acetylcholine receptor M3, ChAT expression, acetylcholine levels and acetylcholine binding were measured in a human pulmonary mucoepidermoid carcinoma cell line (H292) stimulated with CSE. We performed ChAT/RNA interference experiments in H292 cells stimulated with CSE to study the role of ChAT/acetylcholine in MUC5AC production. The effects of Hemicholinium-3 (HCh-3) (50 μM) (a potent and selective choline uptake blocker) and Tiotropium bromide (Spiriva ® ) (100 nM), alone o…

Pleural Mesothelial Cells Express Both BLT2 and PPARα and Mount an Integrated Response to Pleural Leukotriene B4

Abstract Leukotriene B4 (LTB4) plays a crucial role in the recruitment of neutrophils into the pleural space. We identified for the first time the mechanisms by which LTB4 interacts with mesothelial cells and recruits neutrophils in the pleural compartment. Primary pleural mesothelial cells express both the proinflammatory receptor for LTB4 BLT2, and the anti-inflammatory receptor for LTB4, PPARα. Parapneumonic pleural effusions highly increase BLT2 expression and, via BLT2 activation, increase the adhesion between mesothelial cells and neutrophils and the expression of ICAM-1 on mesothelial cells. The block of PPARα further increases both cell adhesion and ICAM-1 expression. BLT2 activatio…