0000000001179942
AUTHOR
Bruno Balbi
TLR4 and NOD1 increase in stable COPD of increasing severity. Relationship with tissutal bacterial load
Background: The immune host response related to bacterial and viral infections in the airways and lung of COPD patients is unclear. Objectives: To investigate the expression of anti-bacterial and anti-viral antigens in bronchial biopsies and lung parenchyma of stable COPD patients in relation to bacterial load. Methods: Immunohistochemical (IHC) and qRT-PCR-expression of TLR2-3-4-7-8-9, NOD1, NOD2, MYD88, TRIF, TIRAP, pIRAK1, IRAK4, IRF3, pIRF3, IRF7, pIRF7, RIG1, MDA5, LGP2, MAVS, STING, DAI, IFNα and IFNβ was measured in bronchial mucosa in patients with mild/moderate (n=16), severe/very severe (n=18) stable COPD, control smokers (n=12) and control non-smokers (n=12). Selected relevant an…
High-resolution computed tomography quantitation of emphysema is correlated with selected lung function values in stable COPD
<b><i>Background:</i></b> The literature shows conflicting results when high-resolution computed tomography (HRCT) scores of emphysema were correlated with different indices of airflow obstruction. <b><i>Objectives:</i></b> We correlated HRCT scores of emphysema with different indices of airflow obstruction. <b><i>Methods:</i></b> We performed HRCT of the chest in 59 patients, all smokers or ex-smokers, with stable chronic obstructive pulmonary disease of different severity [GOLD stages I–IV; mean age ± SD 67.8 ± 7.3 years; pack/years 51.0 ± 34.6; percent predicted forced expiratory volume in 1 s (FEV<sub>1</su…
Hsp60 and Hsp10 down-regulation predicts bronchial epithelial carcinogenesis in smokers with chronic obstructive pulmonary disease.
BACKGROUND. The relation between smoking, chronic obstructive pulmonary disease (COPD), and lung cancer (LC) is an open field of investigation. A higher frequency of adenocarcinoma has been reported in patients with COPD. Heat shock proteins (Hsps) are implicated in tumoral cell growth and differentiation. The aim of the present study was to investigate the expression of Hsp60 and Hsp10 in bronchial biopsies from smokers with COPD and in 10 lung cancer patients and to evaluate the association between Hsps expression and carcinogenetic steps of LC. METHODS. An immunohistochemical study was performed for Hsp60 and Hsp10 in bronchial biopsies from 35 COPD (postbronchodilator forced expiratory …
Bacterial and viral infections and related inflammatory responses in chronic obstructive pulmonary disease
Abstract In chronic obstructive pulmonary disease (COPD) patients, bacterial and viral infections play a relevant role in worsening lung function and, therefore, favour disease progression. The inflammatory response to lung infections may become a specific indication of the bacterial and viral infections. We here review data on the bacterial–viral infections and related airways and lung parenchyma inflammation in stable and exacerbated COPD, focussing our attention on the prevalent molecular pathways in these different clinical conditions. The roles of macrophages, autophagy and NETosis are also briefly discussed in the context of lung infections in COPD. Controlling their combined response…
Association of increased CCL5 and CXCL7 chemokine expression with neutrophil activation in severe stable COPD
BACKGROUND: Increased numbers of activated neutrophils have been reported in the bronchial mucosa of patients with stable chronic obstructive pulmonary disease (COPD), particularly in severe disease. OBJECTIVES: To investigate the expression of neutrophilic chemokines and adhesion molecules in bronchial biopsies from patients with stable COPD of different severity (GOLD stages I-IV) compared with age-matched control subjects, smokers with normal lung function and never smokers. METHODS: The expression of CCL5, CXCL1, 5, 6, 7 and 8, CXCR1, CXCR2, CD11b and CD44 was measured in the bronchial mucosa using immunohistochemistry, confocal immunofluorescence, real-time quantitative polymerase chai…
<p>Bacterial load and inflammatory response in sputum of alpha-1 antitrypsin deficiency patients with COPD</p>
Background Airway inflammation may drive the progression of chronic obstructive pulmonary disease (COPD) associated with alpha-1 antitrypsin deficiency (AATD), but the relationship between airway microbiota and inflammation has not been investigated. Methods We studied 21 non-treated AATD (AATD-noT) patients, 20 AATD-COPD patients under augmentation therapy (AATD-AT), 20 cigarette smoke-associated COPD patients, 20 control healthy smokers (CS) and 21 non-smokers (CON) with normal lung function. We quantified sputum inflammatory cells and inflammatory markers (IL-27, CCL3, CCL5, CXCL8, LTB4, MPO) by ELISA, total bacterial load (16S) and pathogenic bacteria by qRT-PCR. Results AATD-AT patient…
Phospho-p38 MAPK expression in COPD patients and asthmatics and in challenged bronchial epithelium
<b><i>Background:</i></b> The role of mitogen-activated protein kinases (MAPK) in regulating the inflammatory response in the airways of patients with chronic obstructive pulmonary disease (COPD) and asthmatic patients is unclear. <b><i>Objectives:</i></b> To investigate the expression of activated MAPK in lungs of COPD patients and in bronchial biopsies of asthmatic patients and to study MAPK expression in bronchial epithelial cells in response to oxidative and inflammatory stimuli. <b><i>Methods:</i></b> Immunohistochemical expression of phospho (p)-p38 MAPK, p-JNK1 and p-ERK1/2 was measured in bronchial mucosa in pat…
Bronchial inflammation and bacterial load in stable COPD is associated with TLR4 overexpression.
Toll-like receptors (TLRs) and nucleotide-binding oligomerisation domain (NOD)-like receptors (NLRs) are two major forms of innate immune sensors but their role in the immunopathology of stable chronic obstructive pulmonary disease (COPD) is incompletely studied. Our objective here was to investigate TLR and NLR signalling pathways in the bronchial mucosa in stable COPD.Using immunohistochemistry, the expression levels of TLR2, TLR4, TLR9, NOD1, NOD2, CD14, myeloid differentiation primary response gene 88 (MyD88), Toll-interleukin-1 receptor domain-containing adaptor protein (TIRAP), and the interleukin-1 receptor-associated kinases phospho-IRAK1 and IRAK4 were measured in the bronchial muc…
Airway inflammation in healthy smokers
Cigarette smoking is a risk factor associated with lung cancer and many other neoplasms of various organs, coronary artery disease and numerous vascular disorders, Chronic Obstructive Pulmonary Disease (COPD) and other types of lung diseases [13]. Much work has been done on the in vitro and ex vivo carcinogenetic effects of tobacco smoking while the effects of smoking on innate and adaptive immune function have been studied to a lesser degree. Recent data suggests that cigarette smoke alters the functions of the immune system and increases susceptibility to viral and bacterial infections [4-6]. In the respiratory system along the last years many studies have depicted the changes induced by …
Pro-and anti-fibrotic molecule balance in the bronchial mucosa of stable COPD patients
Background: The mechanisms of inducing fibrotic events and remodeling in the airways of COPD are incompletely studied. Objectives: To investigate the expression of cytokines involved in the pro- and anti-fibrotic events in stable COPD. Methods: Expression of CTGF, TGFβ1-2-3, TGFβRI, TGFβRII, LTBP-1, TRAP-1, BAMBI, PP2Cα, Smad2-3-6-7, pSmad2, pSmad3, pro-collagen-I and collagen-I was measured in the bronchial mucosa using immunohistochemistry and RT-qPCR. Results: TGFβ1 was increased in the epithelium and TGFβ3 in the submucosa of healthy smokers and mild/moderate COPD compared to healthy non-smokers. In all smokers and patients with COPD TGFβ3+ cells in the submucosa correlated significantl…
HSP60 activity on human bronchial epithelial cells
HSP60 has been implicated in chronic inflammatory disease pathogenesis, including chronic obstructive pulmonary disease (COPD), but the mechanisms by which this chaperonin would act are poorly understood. A number of studies suggest a role for extracellular HSP60, since it can be secreted from cells and bind Toll-like receptors; however, the effects of this stimulation have never been extensively studied. We investigated the effects (pro- or anti-inflammatory) of HSP60 in human bronchial epithelial cells (16-HBE) alone and in comparison with oxidative, inflammatory, or bacterial challenges. 16-HBE cells were cultured for 1–4 h in the absence or presence of HSP60, H2O2, lipopolysaccharide (…
Downregulation of IL-27 bronchial epithelial expression by heat-shock protein-60
Background Heat-shock protein 60 (Hsp60) is ubiquitous and highly conserved Molecular chaperone. Hsp60 plays an important role in protein folding, inflammation, and tissue repair. We previously reported increased levels of HSP60 in COPD patients, suggesting a role for HSP60 in the inflammatory response in COPD. This study is aimed to evaluate the HSP60 immunomodulatory activity and Th1/Tc1 cytokines (IL-27/INFγ) production in Human Bronchial Epithelial cells line (16HBE). Methods 16HBE were plated in 6 wells plate with Dulbecco’s modified Minimum Essential Medium (DMEM) and exposed to various concentrations of HSP60 protein (1 ng/mL, 100 ng/mL and 1 µg/mL) for 8 and 24 hours. Induction of H…
Extracorporeal shock waves increase markers of cellular proliferation in primary bronchial fibroblasts of COPD patients
COPD is due to a remodeling of small airways and destruction of the lung parenchyma with loss of the alveolar attachment as a result of pulmonary emphysema. Treatment of connective tissue fibroblasts with extracorporeal shock waves (ESW) increases their cellular proliferation and differentiation. To date no studies are available on ESW treatment of human primary bronchial fibroblasts from COPD and control subjects. Primary bronchial fibroblasts were obtained from bronchial biopsies from three patients with mild/moderate COPD and 3 control smokers with normal lung function. After stabilization for 24h, 1 ml of cell suspension (106 cells) from COPD and controls was treated in 2 ml tubes with …
Extracorporeal Shock Waves Increase Markers of Cellular Proliferation in Bronchial Epithelium and in Primary Bronchial Fibroblasts of COPD Patients
Chronic obstructive pulmonary disease (COPD) is due to structural changes and narrowing of small airways and parenchymal destruction (loss of the alveolar attachment as a result of pulmonary emphysema), which all lead to airflow limitation. Extracorporeal shock waves (ESW) increase cell proliferation and differentiation of connective tissue fibroblasts. To date no studies are available on ESW treatment of human bronchial fibroblasts and epithelial cells from COPD and control subjects. We obtained primary bronchial fibroblasts from bronchial biopsies of 3 patients with mild/moderate COPD and 3 control smokers with normal lung function. 16HBE cells were also studied. Cells were treated with a…
Nerve ablation after bronchial thermoplasty and sustained improvement in severe asthma
Abstract Background Bronchial thermoplasty (BT) is a non-pharmacological intervention for severe asthma whose mechanism of action is not completely explained by a reduction of airway smooth muscle (ASM). In this study we analyzed the effect of BT on nerve fibers and inflammatory components in the bronchial mucosa at 1 year. Methods Endobronchial biopsies were obtained from 12 subjects (mean age 47 ± 11.3 years, 50% male) with severe asthma. Biopsies were performed at baseline (T0) and after 1 (T1), 2 (T2) and 12 (T12) months post-BT, and studied with immunocytochemistry and microscopy methods. Clinical data including Asthma Quality of Life Questionnaire (AQLQ) and Asthma Control Questionnai…
Hsp10 nuclear localization and changes in lung cells response to cigarette smoke suggest novel roles for this chaperonin
Heat-shock protein (Hsp)10 is the co-chaperone for Hsp60 inside mitochondria, but it also resides outside the organelle. Variations in its levels and intracellular distribution have been documented in pathological conditions, e.g. cancer and chronic obstructive pulmonary disease (COPD). Here, we show that Hsp10 in COPD undergoes changes at the molecular and subcellular levels in bronchial cells from human specimens and derived cell lines, intact or subjected to stress induced by cigarette smoke extract (CSE). Noteworthy findings are: (i) Hsp10 occurred in nuclei of epithelial and lamina propria cells of bronchial mucosa from non-smokers and smokers; (ii) human bronchial epithelial (16HBE) a…
Bacterial-viral load and the immune response in stable and exacerbated COPD: significance and therapeutic prospects.
Silvestro Ennio D’Anna,1 Bruno Balbi,2 Francesco Cappello,3,4 Mauro Carone,2 Antonino Di Stefano21Department of Rehabilitation, Cardiorespiratory Unit, Fondazione Istituto G. Giglio di Cefalù, 2Pneumology Unit and Laboratory of Cytoimmunopathology of Heart and Lung, Fondazione Salvatore Maugeri, IRCCS, Veruno (NO) and Cassano delle Murge (BA), 3Human Anatomy Section, Department of Experimental Biomedicine and Clinical Neuroscience, University of Palermo, Palermo, Italy; 4Euro-Mediterranean Institute of Science and Technology, Palermo, ItalyAbstract: Chronic obstructive pulmonary disease (COPD) is characterized by persistent airflow limitation and an abnormal inflammatory respon…
Bacterial&ndash;viral load and the immune response in stable and exacerbated COPD: significance and therapeutic prospects
Silvestro Ennio D&rsquo;Anna,1 Bruno Balbi,2 Francesco Cappello,3,4 Mauro Carone,2 Antonino Di Stefano21Department of Rehabilitation, Cardiorespiratory Unit, Fondazione Istituto G. Giglio di Cefal&ugrave;, 2Pneumology Unit and Laboratory of Cytoimmunopathology of Heart and Lung, Fondazione Salvatore Maugeri, IRCCS, Veruno (NO) and Cassano delle Murge (BA), 3Human Anatomy Section, Department of Experimental Biomedicine and Clinical Neuroscience, University of Palermo, Palermo, Italy; 4Euro-Mediterranean Institute of Science and Technology, Palermo, ItalyAbstract: Chronic obstructive pulmonary disease (COPD) is characterized by persistent airflow limitation and an abnormal inflammator…
TGF-β Signaling Pathways in Different Compartments of the Lower Airways of Patients With Stable COPD
Background: The expression and localization of transforming growth factor-β (TGF-β) pathway proteins in different compartments of the lower airways of patients with stable COPD is unclear. We aimed to determine TGF-β pathway protein expression in patients with stable COPD. Methods: The expression and localization of TGF-β pathway components was measured in the bronchial mucosa and peripheral lungs of patients with stable COPD (n = 44), control smokers with normal lung function (n = 24), and control nonsmoking subjects (n = 11) using immunohistochemical analysis. Results: TGF-β1, TGF-β3, and connective tissue growth factor expression were significantly decreased in the bronchiolar epithelium…
T helper type 17-related cytokine expression is increased in the bronchial mucosa of stable chronic obstructive pulmonary disease patients.
Summary There are increased numbers of activated T lymphocytes in the bronchial mucosa of stable chronic obstructive pulmonary disease (COPD) patients. T helper type 17 (Th17) cells release interleukin (IL)-17 as their effector cytokine under the control of IL-22 and IL-23. Furthermore, Th17 numbers are increased in some chronic inflammatory conditions. To investigate the expression of interleukin (IL)-17A, IL-17F, IL-21, IL-22 and IL-23 and of retinoic orphan receptor RORC2, a marker of Th17 cells, in bronchial biopsies from patients with stable COPD of different severity compared with age-matched control subjects. The expression of IL-17A, IL-17F, IL-21, IL-22, IL-23 and RORC2 was measure…
Convergent sets of data from in vivo and in vitro methods point to an active role of Hsp60 in chronic obstructive pulmonary disease pathogenesis.
BackgroundIt is increasingly clear that some heat shock proteins (Hsps) play a role in inflammation. Here, we report results showing participation of Hsp60 in the pathogenesis of chronic obstructive pulmonary diseases (COPD), as indicated by data from both in vivo and in vitro analyses.Methods and resultsBronchial biopsies from patients with stable COPD, smoker controls with normal lung function, and non-smoker controls were studied. We quantified by immunohistochemistry levels of Hsp10, Hsp27, Hsp40, Hsp60, Hsp70, Hsp90, and HSF-1, along with levels of inflammatory markers. Hsp10, Hsp40, and Hsp60 were increased during progression of disease. We found also a positive correlation between th…