20 research outputs found
Beta defensin-2 is reduced in central but not in distal airways of smoker COPD patients
Background: Altered pulmonary defenses in chronic obstructive pulmonary disease (COPD) may promote distal airways bacterial colonization. The expression/activation of Toll Like receptors (TLR) and beta 2 defensin (HBD2) release by epithelial cells crucially affect pulmonary defence mechanisms. Methods: The epithelial expression of TLR4 and of HBD2 was assessed in surgical specimens from current smokers COPD (s-COPD; n = 17), ex-smokers COPD (ex-s-COPD; n = 8), smokers without COPD (S; n = 12), and from non-smoker non-COPD subjects (C; n = 13). Results: In distal airways, s-COPD highly expressed TLR4 and HBD2. In central airways, S and s-COPD showed increased TLR4 expression. Lower HBD2 expression was observed in central airways of s-COPD when compared to S and to ex-s-COPD. s-COPD had a reduced HBD2 gene expression as demonstrated by real-time PCR on micro-dissected bronchial epithelial cells. Furthermore, HBD2 expression positively correlated with FEV1/FVC ratio and inversely correlated with the cigarette smoke exposure. In a bronchial epithelial cell line (16 HBE) IL-1β significantly induced the HBD2 mRNA expression and cigarette smoke extracts significantly counteracted this IL-1 mediated effect reducing both the activation of NFkB pathway and the interaction between NFkB and HBD2 promoter. Conclusions: This study provides new insights on the possible mechanisms involved in the alteration of innate immunity mechanisms in COPD. © 2012 Pace et al
“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-b 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-b and fluticasone propionate on leptin
receptor expression. Finally, the role of leptin on TGF-b release
and cell proliferation was analyzed. Ex vivo we investigated the
presence of leptin/leptin receptor in the epithelium of bronchial
biopsy specimens from subjects with asthma of various
severities and from healthy volunteers, and some features of
airway remodeling, such as reticular basement membrane
(RBM) thickness and TGF-b expression in the epithelium, were
assessed.
Results: In vitro bronchial epithelial cells express leptin/leptin
receptor. TGF-b decreased and fluticasone propionate increased
leptin receptor expression, and leptin decreased the spontaneous
release of TGF-b and increased cell proliferation. Ex vivo the
bronchial epithelium of subjects with mild, uncontrolled,
untreated asthma showed a decrease expression of leptin and its
receptor and an increased RBM thickness and TGF-b
expression when compared with values seen in healthy
volunteers. Furthermore, severe asthma was associated with a
reduced expression of leptin and its receptor and an increased
RBM thickness with unaltered TGF-b expression.
Conclusions: Decreased expression of leptin/leptin receptor
characterizes severe asthma and is associated with airway
remodeling features
Cigarette smoke alters IL-33 expression and release in airway epithelial cells
AbstractAirway epithelium is a regulator of innate immune responses to a variety of insults including cigarette smoke. Cigarette smoke alters the expression and the activation of Toll Like Receptor 4 (TLR4), an innate immunity receptor. IL-33, an alarmin, increases innate immunity Th2 responses. The aims of this study were to explore whether mini-bronchoalveolar lavage (mini-BAL) or sera from smokers have altered concentrations of IL-33 and whether cigarette smoke extracts (CSE) alter both intracellular expression (mRNA and protein) and release of IL-33 in bronchial epithelial cells. The role of TLR4 in the expression of IL-33 was also explored.Mini-BALs, but not sera, from smokers show reduced concentrations of IL-33. The expression of IL-33 was increased also in bronchial epithelium from smokers. 20% CSE reduced IL-33 release but increased the mRNA for IL-33 by real time PCR and the intracellular expression of IL-33 in bronchial epithelial cells as confirmed by flow cytometry, immunocytochemistry and western blot analysis. The effect of CSE on IL-33 expression was also observed in primary bronchial epithelial cells. IL-33 expression was mainly concentrated within the cytoplasm of the cells. LPS, an agonist of TLR4, reduced IL-33 expression, and an inhibitor of TLR4 increased the intracellular expression of IL-33. In conclusion, the release of IL-33 is tightly controlled and, in smokers, an altered activation of TLR4 may lead to an increased intracellular expression of IL-33 with a limited IL-33 release
Assessment of the exposure to Allura Red colour from the consumption of red juice-based and red soft drinks in Italy
Release of transforming growth factor-beta (TGF-β) and fibronectin by alveolar macrophages in airway diseases
Asthma and chronic bronchitis are associated with airway remodelling, and airway macrophages are present in bronchial inflammation. TGF-β and fibronectin released by alveolar macrophages possess a fibrogenic potency. The potential role of alveolar macrophages in airway remodelling was studied in asthma and chronic bronchitis by the release of TGF-β and fibronectin. Alveolar macrophages were isolated by bronchoalveolar lavage in 14 control subjects, 14 asthmatics and 14 chronic bronchitics. The spontaneous and lipopolysaccharide (LPS)- or concanavalin A (Con A)-induced release of TGF-β and fibronectin was measured by ELISA. Alveolar macrophages from chronic bronchitics spontaneously release greater amounts of TGF-β and fibronectin than those from asthmatic and control subjects. Alveolar macrophages from asthmatics release greater amounts of TGF-β and fibronectin than those from control subjects. The spontaneous release of TGF-β is significantly correlated with that of fibronectin. Fibronectin release was significantly reduced after LPS stimulation, and TGF-β release was significantly increased after LPS stimulation, except in chronic bronchitis patients. Con A increased the release of TGF-β in cells from normal subjects. This study suggests that activated macrophages play a role in airway remodelling in chronic bronchitis and to a lesser extent in asthma
Notch-1 signaling activation sustains overexpression of interleukin 33 in the epithelium of nasal polyps
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 (by flow cytometry), and p-CREB transcription factor (by western blot analysis). Results: Ex vivo (a) in normal epithelium, the expression of Notch-1 and IL-33 were higher in NA-CRSwNP than in A-CRSwNP; (b) in metaplastic epithelium, the expression of Notch-1, Jagged-1, and IL-33 were higher in NA-CRSwNP than in A-CRSwNP; (c) in hyperplastic epithelium, the expression of Notch-1, Jagged-1, and IL-33 were higher in A-CRSwNP than in NA-CRSwNP; and (d) in basal epithelial cells, no differences were observed in the expression of Jagged-1, IL-33, and Notch-1. The expression of Notch-1 significantly correlated with the expression of IL-33. In vitro, stimulation of Notch-1 with Jagged-1 induced the expression of (a) Jagged-1; (b) IL-33; and (c) p-CREB transcription factor. The inhibitor of Notch-1, DAPT, reduced all the effects of Jagged-1 on nasal epithelial cells. Conclusions: The data herein provided support, for the first time, a putative role of Notch-1/Jagged-1 signaling in the overexpression of IL-33 in the epithelium of nasal polyps from patients with CRSwNP