scholarly journals Airwayβ-Defensin-1 Protein Is Elevated in COPD and Severe Asthma

2015 ◽  
Vol 2015 ◽  
pp. 1-8 ◽  
Author(s):  
Katherine J. Baines ◽  
Thomas K. Wright ◽  
Jodie L. Simpson ◽  
Vanessa M. McDonald ◽  
Lisa G. Wood ◽  
...  
Keyword(s):  
Severe Asthma ◽  
Chronic Obstructive ◽  
Healthy Controls ◽  
Obstructive Pulmonary Disease ◽  
Bronchial Epithelial ◽  
Receiver Operating Characteristic Curves ◽  
Asthma Patients ◽  
Inflammatory Phenotype ◽  
Primary Bronchial Epithelial Cells

Background. Innate immune antimicrobial peptides, includingβ-defensin-1, promote the chemotaxis and activation of several immune cells. The role ofβ-defensin-1 in asthma and chronic obstructive pulmonary disease (COPD) remains unclear.Methods. Induced sputum was collected from healthy controls and individuals with asthma or COPD.β-defensin-1 protein in sputum supernatant was quantified by ELISA. Biomarker potential was examined using receiver operating characteristic curves.β-defensin-1 release from primary bronchial epithelial cells (pBECs) was investigated in culture with and without cigarette smoke extract (CSE).Results. Airwayβ-defensin-1 protein was elevated in COPD participants compared to asthma participants and healthy controls. Inflammatory phenotype had no effect onβ-defensin-1 levels in asthma or COPD.β-defensin-1 protein was significantly higher in severe asthma compared to controlled and uncontrolled asthma.β-defensin-1 protein could predict the presence of COPD from both healthy controls and asthma patients. Exposure of pBECs to CSE decreasedβ-defensin-1 production in healthy controls; however in pBECs from COPD participants the level ofβ-defensin-1 remanied unchanged.Conclusions. Elevatedβ-defensin-1 protein is a feature of COPD and severe asthma regardless of inflammatory phenotype.β-defensin-1 production is dysregulated in the epithelium of patients with COPD and may be an effective biomarker and potential therapeutic target.

scholarly journals miR-146a-5p plays an essential role in the aberrant epithelial–fibroblast cross-talk in COPD

2017 ◽  
Vol 49 (5) ◽  
pp. 1602538 ◽  
Author(s):  
Emmanuel T. Osei ◽  
Laura Florez-Sampedro ◽  
Hataitip Tasena ◽  
Alen Faiz ◽  
Jacobien A. Noordhoek ◽  
...  
Keyword(s):  
Airway Epithelial Cells ◽  
Lung Fibroblasts ◽  
Chronic Obstructive ◽  
Airway Epithelial ◽  
Single Nucleotide ◽  
Obstructive Pulmonary Disease ◽  
Bronchial Epithelial ◽  
Lung Epithelial ◽  
Inflammatory Phenotype

We previously reported that epithelial-derived interleukin (IL)-1α drives fibroblast-derived inflammation in the lung epithelial–mesenchymal trophic unit. Since miR-146a-5p has been shown to negatively regulate IL-1 signalling, we investigated the role of miR-146a-5p in the regulation of IL-1α-driven inflammation in chronic obstructive pulmonary disease (COPD).Human bronchial epithelial (16HBE14o-) cells were co-cultured with control and COPD-derived primary human lung fibroblasts (PHLFs), and miR-146a-5p expression was assessed with and without IL-1α neutralising antibody. Genomic DNA was assessed for the presence of the single nucleotide polymorphism (SNP) rs2910164. miR-146a-5p mimics were used for overexpression studies to assess IL-1α-induced signalling and IL-8 production by PHLFs.Co-culture of PHLFs with airway epithelial cells significantly increased the expression of miR-146a-5p and this induction was dependent on epithelial-derived IL-1α. miR-146a-5p overexpression decreased IL-1α-induced IL-8 secretion in PHLFs via downregulation of IL-1 receptor-associated kinase-1. In COPD PHLFs, the induction of miR-146a-5p was significantly less compared with controls and was associated with the SNP rs2910164 (GG allele) in the miR-146a-5p gene.Our results suggest that induction of miR-146a-5p is involved in epithelial–fibroblast communication in the lungs and negatively regulates epithelial-derived IL-1α induction of IL-8 by fibroblasts. The decreased levels of miR-146a-5p in COPD fibroblasts may induce a more pro-inflammatory phenotype, contributing to chronic inflammation in COPD.

Pulmonary Toxicity of Realistic Alveolar Deposition Concentrations of Ultrafine Particulate Matters in Human Normal Bronchial Epithelial Cell

2021 ◽  
Author(s):  
Chia-Hua Lin ◽  
Shih-Chun Candice Lung ◽  
Yi-Chun Chen ◽  
Lung-Chun Wang
Keyword(s):  
Bronchial Epithelial Cell ◽  
Chronic Obstructive ◽  
Heme Oxygenase 1 ◽  
Obstructive Pulmonary Disease ◽  
Bronchial Epithelial ◽  
Low Concentrations ◽  
Ros Accumulation ◽  
Normal Bronchial Epithelial Cell ◽  
Normal Human

Abstract Air pollution is a major worldwide concern, and exposure to particulate matter (PM) can increase the risks of pulmonary diseases. Normal human bronchial epithelial cells were applied to clarify the role of ultrafine PM (UFPM) in the pathogenesis of pulmonary toxic effects with realistic alveolar deposition doses. The UFPM used in this research originated from vehicular emissions and coal combustion. UFPM exposure of up to 72 h was found to induce significant time- and concentration-dependent decreases in cell viability. Exposure to UFPM increased reactive oxygen species (ROS) accumulation through heme oxygenase-1 (HO-1) inhibition and induced massive oxidative stress that increased the interleukin-8 (IL-8) expression. UFPM also reduced the pulmonary trans-epithelial electrical resistance through the depletion of zonula occludens (ZO) proteins. Finally, UFPM decreased the α1-antitrypsin (A1AT) expression, which implies high risk of chronic obstructive pulmonary disease (COPD). The evidence demonstrates that exposure to UFPM, even at very low concentrations, may affect the functions of the respiratory system.

Cigarette smoke irreversibly modifies glutathione in airway epithelial cells

2007 ◽  
Vol 293 (5) ◽  
pp. L1156-L1162 ◽  
Author(s):  
Marco van der Toorn ◽  
Maria P. Smit-de Vries ◽  
Dirk-Jan Slebos ◽  
Harold G. de Bruin ◽  
Nicolas Abello ◽  
...  
Keyword(s):  
Epithelial Cells ◽  
Cigarette Smoke ◽  
A549 Cells ◽  
Airway Epithelial Cells ◽  
Chronic Obstructive ◽  
Airway Epithelial ◽  
Obstructive Pulmonary Disease ◽  
Bronchial Epithelial ◽  
Gsh Metabolism ◽  
Primary Bronchial Epithelial Cells

In patients with chronic obstructive pulmonary disease (COPD), an imbalance between oxidants and antioxidants is acknowledged to result in disease development and progression. Cigarette smoke (CS) is known to deplete total glutathione (GSH + GSSG) in the airways. We hypothesized that components in the gaseous phase of CS may irreversibly react with GSH to form GSH derivatives that cannot be reduced (GSX), thereby causing this depletion. To understand this phenomenon, we investigated the effect of CS on GSH metabolism and identified the actual GSX compounds. CS and H2O2 (control) deplete reduced GSH in solution [Δ = −54.1 ± 1.7 μM ( P < 0.01) and −39.8 ± 0.9 μM ( P < 0.01), respectively]. However, a significant decrease of GSH + GSSG was observed after CS (Δ = −75.1 ± 7.6 μM, P < 0.01), but not after H2O2. Exposure of A549 cells and primary bronchial epithelial cells to CS decreased free sulfhydryl (-SH) groups (Δ = −64.2 ± 14.6 μM/mg protein, P < 0.05) and irreversibly modified GSH + GSSG (Δ = −17.7 ± 1.9 μM, P < 0.01) compared with nonexposed cells or H2O2 control. Mass spectrometry (MS) showed that GSH was modified to glutathione-aldehyde derivatives. Further MS identification showed that GSH was bound to acrolein and crotonaldehyde and another, yet to be identified, structure. Our data show that CS does not oxidize GSH to GSSG but, rather, reacts to nonreducible glutathione-aldehyde derivatives, thereby depleting the total available GSH pool.

Role of exhaled nitric oxide in predicting steroid response in chronic obstructive pulmonary disease

2010 ◽  
Vol 151 (51) ◽  
pp. 2083-2088 ◽  
Author(s):  
Balázs Antus
Keyword(s):  
Nitric Oxide ◽  
Chronic Obstructive Pulmonary Disease ◽  
Pulmonary Disease ◽  
Exhaled Nitric Oxide ◽  
Chronic Obstructive ◽  
Obstructive Pulmonary Disease ◽  
Steroid Response

A kilégzett levegőben mérhető nitrogén-monoxid a legszélesebb körben vizsgált légúti biomarker. A stabil állapotú krónikus obstruktív tüdőbetegségben a kilégzett nitrogén-monoxid-szint hasonló vagy csak kismértékben emelkedett az egészségesekhez képest. Mivel a nitrogén-monoxid-szint szoros összefüggést mutat a légúti eosinophilia mértékével, és mivel az eosinophil típusú légúti gyulladás szteroidokra érzékenyebb, az emelkedett nitrogén-monoxid-szinttel rendelkező betegek jobb válaszkészséget mutatnak az inhalációs vagy szisztémás kortikoszteroidkezelésre. A krónikus obstruktív tüdőbetegség akut exacerbatiója során a kilégzett nitrogén-monoxid szintje megemelkedik, majd ennek kezelése után csökken. Mivel a nitrogén-monoxid-szint és a kezelés során elért légzésfunkciós javulás szoros korrelációt mutat egymással, a nitrogén-monoxid-méréssel a terápiás válasz megjósolható. Összefoglalva: a nitrogén-monoxid-méréssel a krónikus obstruktív tüdőbetegségben szenvedő betegek olyan alcsoportját lehet elkülöníteni, amelynek szteroidérzékenysége nagyobb. Orv. Hetil., 2010, 151, 2083–2088.

Participation of ABCA1 transporter in development of chronic obstructive pulmonary disease

2020 ◽  
Vol 28 (3) ◽  
pp. 360-370
Author(s):  
Stanislav N. Kotlyarov ◽  
Anna A. Kotlyarova
Keyword(s):  
Chronic Obstructive Pulmonary Disease ◽  
Pulmonary Disease ◽  
Significant Contribution ◽  
Modern Medicine ◽  
Lipid Homeostasis ◽  
Chronic Obstructive ◽  
Obstructive Pulmonary Disease ◽  
Reverse Transport ◽  
Current Paradigm

Despite all achievements of the modern medicine, the problem of chronic obstructive pulmonary disease (COPD) does not lose its relevance. The current paradigm suggests a key role of macrophages in inflammation in COPD. Macrophages are known to be heterogeneous in their functions. This heterogeneity is determined by their immunometabolic profile and also by peculiarities of lipid homeostasis of cells. Aim. To analyze the role of the ABCA1 transporter, a member of the ABC A subfamily, in the pathogenesis of COPD. The expression of ABCA1 in lung tissues is on the second place after the liver, which shows the important role of the carrier and of lipid homeostasis in the function of lungs. Analysis of the literature shows that participation of the transporter in inflammation consists in regulation of the content of cholesterol in the lipid rafts of the membranes, in phagocytosis and apoptosis. Conclusion. Through regulation of the process of reverse transport of cholesterol in macrophages of lungs, ABCA1 can change their inflammatory response, which makes a significant contribution to the pathogenesis of COPD.

scholarly journals The Ability of Metabolomics to Discriminate Non-Small-Cell Lung Cancer Subtypes Depends on the Stage of the Disease and the Type of Material Studied

Cancers ◽  
2021 ◽  
Vol 13 (13) ◽  
pp. 3314
Author(s):  
Tomasz Kowalczyk ◽  
Joanna Kisluk ◽  
Karolina Pietrowska ◽  
Joanna Godzien ◽  
Miroslaw Kozlowski ◽  
...  
Keyword(s):  
Metabolic Pathways ◽  
Early Stage ◽  
Chronic Obstructive ◽  
Liquid Chromatography Mass Spectrometry ◽  
Obstructive Pulmonary Disease ◽  
Cell Lung Carcinoma ◽  
Cancer Subtypes ◽  
Inflammatory State ◽  
Nsclc Patients

Identification of the NSCLC subtype at an early stage is still quite sophisticated. Metabolomics analysis of tissue and plasma of NSCLC patients may indicate new, and yet unknown, metabolic pathways active in the NSCLC. Our research characterized the metabolomics profile of tissue and plasma of patients with early and advanced NSCLC stage. Samples were subjected to thorough metabolomics analyses using liquid chromatography-mass spectrometry (LC-MS) technique. Tissue and/or plasma samples from 137 NSCLC patients were analyzed. Based on the early stage tissue analysis, more than 200 metabolites differentiating adenocarcinoma (ADC) and squamous cell lung carcinoma (SCC) subtypes as well as normal tissue, were identified. Most of the identified metabolites were amino acids, fatty acids, carnitines, lysoglycerophospholipids, sphingomyelins, plasmalogens and glycerophospholipids. Moreover, metabolites related to N-acyl ethanolamine (NAE) biosynthesis, namely glycerophospho (N-acyl) ethanolamines (GP-NAE), which discriminated early-stage SCC from ADC, have also been identified. On the other hand, the analysis of plasma of chronic obstructive pulmonary disease (COPD) and NSCLC patients allowed exclusion of the metabolites related to the inflammatory state in lungs and the identification of compounds (lysoglycerophospholipids, glycerophospholipids and sphingomyelins) truly characteristic to cancer. Our results, among already known, showed novel, thus far not described, metabolites discriminating NSCLC subtypes, especially in the early stage of cancer. Moreover, the presented results also indicated the activity of new metabolic pathways in NSCLC. Further investigations on the role of NAE biosynthesis pathways in the early stage of NSCLC may reveal new prognostic and diagnostic targets.

Sign in / Sign up

Export Citation Format

Share Document