scholarly journals Interleukin-1α drives the dysfunctional cross-talk of the airway epithelium and lung fibroblasts in COPD

2016 ◽  
Vol 48 (2) ◽  
pp. 359-369 ◽  
Author(s):  
Emmanuel T. Osei ◽  
Jacobien A. Noordhoek ◽  
Tillie L. Hackett ◽  
Anita I.R. Spanjer ◽  
Dirkje S. Postma ◽  
...  
Keyword(s):  
Inflammatory Mediators ◽  
Airway Epithelium ◽  
Fetal Lung ◽  
Bronchial Epithelial Cell ◽  
Airway Epithelial Cells ◽  
Lung Fibroblast ◽  
Lung Fibroblasts ◽  
Chronic Obstructive ◽  
Obstructive Pulmonary Disease ◽  
And Control

Chronic obstructive pulmonary disease (COPD) has been associated with aberrant epithelial–mesenchymal interactions resulting in inflammatory and remodelling processes. We developed a co-culture model using COPD and control-derived airway epithelial cells (AECs) and lung fibroblasts to understand the mediators that are involved in remodelling and inflammation in COPD.AECs and fibroblasts obtained from COPD and control lung tissue were grown in co-culture with fetal lung fibroblast or human bronchial epithelial cell lines. mRNA and protein expression of inflammatory mediators, pro-fibrotic molecules and extracellular matrix (ECM) proteins were assessed.Co-culture resulted in the release of pro-inflammatory mediators interleukin (IL)-8/CXCL8 and heat shock protein (Hsp70) from lung fibroblasts, and decreased expression of ECM molecules (e.g. collagen, decorin) that was not different between control and COPD-derived primary cells. This pro-inflammatory effect was mediated by epithelial-derived IL-1α and increased upon epithelial exposure to cigarette smoke extract (CSE). When exposed to CSE, COPD-derived AECs elicited a stronger IL-1α response compared with control-derived airway epithelium and this corresponded with a significantly enhanced IL-8 release from lung fibroblasts.We demonstrate that, through IL-1α production, AECs induce a pro-inflammatory lung fibroblast phenotype that is further enhanced with CSE exposure in COPD, suggesting an aberrant epithelial–fibroblast interaction in COPD.

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.

scholarly journals 27-Hydroxycholesterol accelerates cellular senescence in human lung resident cells

2016 ◽  
Vol 310 (11) ◽  
pp. L1028-L1041 ◽  
Author(s):  
Yuichiro Hashimoto ◽  
Hisatoshi Sugiura ◽  
Shinsaku Togo ◽  
Akira Koarai ◽  
Kyoko Abe ◽  
...  
Keyword(s):  
Cellular Senescence ◽  
Healthy Subjects ◽  
Tissue Repair ◽  
Airway Epithelial Cells ◽  
Lung Fibroblasts ◽  
Chronic Obstructive ◽  
Prostaglandin E ◽  
Obstructive Pulmonary Disease ◽  
Copd Patients ◽  
Associated Proteins

Cellular senescence is reportedly involved in the pathogenesis of chronic obstructive pulmonary disease (COPD). We previously showed that 27-hydroxycholesterol (27-OHC) is elevated in the airways of COPD patients compared with those in healthy subjects. The aim of this study was to investigate whether lung fibroblasts of COPD patients are senescent and to determine the effects of 27-OHC on senescence of lung resident cells, including fibroblasts and airway epithelial cells. Localization of senescence-associated proteins and sterol 27-hydroxylase was investigated in the lungs of COPD patients by immunohistochemical staining. To evaluate whether 27-OHC accelerates cellular senescence, lung resident cells were exposed to 27-OHC. Senescence markers and fibroblast-mediated tissue repair were investigated in the 27-OHC-treated cells. Expression of senescence-associated proteins was significantly enhanced in lung fibroblasts of COPD patients. Similarly, expression of sterol 27-hydroxylase was significantly upregulated in lung fibroblasts and alveolar macrophages in these patients. Treatment with the concentration of 27-OHC detected in COPD airways significantly augmented expression of senescence-associated proteins and senescence-associated β-galactosidase activity, and delayed cell growth through the prostaglandin E2-reactive nitrogen species pathway. The 27-OHC-treated fibroblasts impaired tissue repair function. Fibroblasts from lungs of COPD patients showed accelerated senescence and were more susceptible to 27-OHC-induced cellular senescence compared with those of healthy subjects. In conclusion, 27-OHC accelerates cellular senescence in lung resident cells and may play a pivotal role in cellular senescence in COPD.

scholarly journals α,β-Unsaturated aldehydes contained in cigarette smoke elicit IL-8 release in pulmonary cells through mitogen-activated protein kinases

2009 ◽  
Vol 296 (5) ◽  
pp. L839-L848 ◽  
Author(s):  
Nadia Moretto ◽  
Fabrizio Facchinetti ◽  
Thomas Southworth ◽  
Maurizio Civelli ◽  
Dave Singh ◽  
...  
Keyword(s):  
Cigarette Smoke ◽  
Neutrophil Infiltration ◽  
Acute Effect ◽  
Airway Epithelial Cells ◽  
Lung Fibroblasts ◽  
Chronic Obstructive ◽  
Tissue Destruction ◽  
Obstructive Pulmonary Disease ◽  
Unsaturated Aldehydes ◽  
Cytokines And Chemokines

Cigarette smoking is the major risk factor for chronic obstructive pulmonary disease (COPD), a syndrome characterized by pulmonary neutrophil infiltration, chronic inflammation, and progressive tissue destruction. We examined here the acute effect of aqueous cigarette smoke extract (CSE) and of two α,β-unsaturated aldehydes (acrolein and crotonaldehyde) contained in CSE in cultured normal human lung fibroblasts and small airway epithelial cells. By examining a panel of 19 cytokines and chemokines, we found that IL-8 release was elevated by CSE as well as by acrolein, whereas other inflammatory mediators were mostly unaffected. CSE-evoked IL-8 release was mimicked by acrolein and crotonaldehyde at concentrations (3–60 μM each) found in CSE and fully prevented by 1 mM α,β-unsaturated aldehydes scavengers N-acetylcysteine (NAC) or sodium 2-mercaptoethanesulfonate. Neither the saturated aldehyde acetaldehyde nor H2O2 evoked IL-8 release. In addition, CSE or crotonaldehyde upregulated the release of IL-8 from alveolar macrophages from both COPD patients and healthy nonsmokers, indicating that this is a response common to cells involved in lung inflammation. CSE-evoked IL-8 release was accompanied by increased phosphorylation of p38 MAPK and ERK1/2. CSE-evoked p38 and ERK1/2 phosphorylation was mimicked by acrolein and inhibited by NAC. IL-8 release elicited by both acrolein and CSE was blocked by pharmacological inhibition of p38 and ERK1/2 phosphorylation. In summary, our data show that α,β-unsaturated aldehydes-evoked phosphorylation of p38 and ERK1/2 underlies IL-8 release elicited by CSE, thus shedding light on the mechanisms through which cigarette smoke can initiate inflammation in the lung.

Mast cell tryptase stimulates human lung fibroblast proliferation via protease-activated receptor-2

2000 ◽  
Vol 278 (1) ◽  
pp. L193-L201 ◽  
Author(s):  
Ian A. Akers ◽  
Maddy Parsons ◽  
Michael R. Hill ◽  
Morley D. Hollenberg ◽  
Shahin Sanjar ◽  
...  
Keyword(s):  
Mast Cells ◽  
Dermal Fibroblast ◽  
Fetal Lung ◽  
Dermal Fibroblasts ◽  
Lung Fibroblasts ◽  
Chronic Obstructive ◽  
Fibroblast Proliferation ◽  
Obstructive Pulmonary Disease ◽  
Human Lung Fibroblast ◽  
Protease Activated Receptor 2

Mast cells play a potentially important role in fibroproliferative diseases, releasing mediators including tryptase that are capable of stimulating fibroblast proliferation and procollagen synthesis. The mechanism by which tryptase stimulates fibroblast proliferation is unclear, although recent studies suggest it can activate protease-activated receptor (PAR)-2. We therefore investigated the role of PAR-2 in tryptase-induced proliferation of human fetal lung and adult lung parenchymal and airway fibroblasts and, for comparative purposes, adult dermal fibroblasts. Tryptase (0.7–70 mU/ml) induced concentration-dependent increases in proliferation of all fibroblasts studied. Antipain, bis(5-amidino-2-benzimidazolyl)methane, and benzamidine inhibited tryptase-induced fibroblast proliferation, demonstrating that proteolytic activity is required for the proliferative effects of tryptase. RT-PCR demonstrated the presence of PAR-2 mRNA, and immunohistochemical staining localized PAR-2 to the cell surface of lung fibroblasts. In addition , specific PAR-2 activating peptides, SLIGKV and SLIGRL, mimicked the proliferative effects of tryptase. In contrast, human dermal fibroblasts only weakly stained with the PAR-2 antibody, PAR-2 mRNA was almost undetectable, and fibroblasts did not respond to PAR-2 activating peptides. These results suggest that tryptase induces lung, but not dermal, fibroblast proliferation via activation of PAR-2 and are consistent with the hypothesis that the release of tryptase from activated mast cells may play an important role in the fibroproliferative response observed in asthma, chronic obstructive pulmonary disease, and patients with pulmonary fibrosis.

ROLE OF PHARMACIST INTERVENTION ON COPD PATIENTS OF SELECTED AREAS IN CHITRADURGA: A KAP STUDY

2019 ◽  
Vol 8 (2) ◽  
Author(s):  
Melvin K Mathews ◽  
Abubaker Siddiq ◽  
Bharathi D R
Keyword(s):  
Illness Perceptions ◽  
Pharmacist Intervention ◽  
Cross Sectional Study ◽  
Chronic Obstructive ◽  
Cross Sectional ◽  
Obstructive Pulmonary Disease ◽  
Copd Patients ◽  
Post Test ◽  
Knowledge Practice ◽  
And Control

Background: Chronic obstructive pulmonary disease (COPD) is preventable and treatable disease state characterized by air flow limitation that is not fully reversible. Severity of the symptoms is increased during exacerbations. Objectives: The purpose of the study is to assess and improve the knowledge regarding COPD among study subjects. Materials and Methods: A Cross-sectional interventional study was carried out among the peoples in selected areas of the Chitradurga city for a period of six months. Result: A total 207 subjects enrolled in the study in that 155 male and 52 females. In our study mean score of post test was more (5.87±1.68) when compare to pre-test (2.63±1.46) which show significant increase in their knowledge after educating them (p=0.000). A total of 207 subjects were enrolled into the study. SPSS Software was used to calculate the statistical estimation. Paired t-test was used to detect the association status of different variables. Conclusion: The relatively good level of COPD awareness needs to be maintained to facilitate future prevention and control of the disease. This study had identified that negative illness perceptions should be targeted, so that they will not avoid patients from seeking for COPD treatment and adhere to it. Key words: Cross sectional study, Knowledge, practice, COPD.

Hazards for Construction Workers

2017 ◽  
Author(s):  
Gavin H. West ◽  
Laura S. Welch
Keyword(s):  
Heavy Metals ◽  
Prevention And Control ◽  
Respiratory Diseases ◽  
Noise Exposure ◽  
Engineered Nanomaterials ◽  
Construction Workers ◽  
Chronic Obstructive ◽  
Obstructive Pulmonary Disease ◽  
And Control ◽  
The Impact

This chapter describes the hazards for construction workers, with a particular focus on injuries as well as exposures to hazardous chemicals and dusts. A section describes hazardous exposures to lead and other heavy metals. Another section describes noise exposure. The impact of musculoskeletal disorders among construction workers is then discussed. A section on respiratory diseases focuses on asbestosis, silicosis, chronic obstructive pulmonary disease, and asthma. Exposures known to cause dermatitis and cancer are reviewed. There is a discussion of engineered nanomaterials as a potential emerging hazard. Various approaches to prevention and control, including regulations and health services, are described.

scholarly journals Effectiveness of a Psychoeducational Group Intervention Carried Out by Nurses for Patients with Depression and Physical Comorbidity in Primary Care: Randomized Clinical Trial

2021 ◽  
Vol 18 (6) ◽  
pp. 2948
Author(s):  
Antonia Raya-Tena ◽  
María Isabel Fernández-San-Martin ◽  
Jaume Martin-Royo ◽  
Rocío Casañas ◽  
Glòria Sauch-Valmaña ◽  
...  
Keyword(s):  
Primary Care ◽  
Clinical Trial ◽  
Depressive Symptoms ◽  
Group Intervention ◽  
Therapeutic Response ◽  
Chronic Obstructive ◽  
Obstructive Pulmonary Disease ◽  
Psychoeducational Group ◽  
One Year ◽  
And Control

The association between physical illness and depression implies a poorer management of chronic disease and a lower response to antidepressant treatments. Our study evaluates the effectiveness of a psychoeducational group intervention led by Primary Care (PC) nurses, aimed at patients of this kind. It is a randomized, multicenter clinical trial with intervention (IG) and control groups (CG), blind response variables, and a one year follow-up. The study included 380 patients ≥50 years of age from 18 PC teams. The participants presented depression (BDI-II > 12) and a physical comorbidity: diabetes mellitus type 2, ischemic heart disease, chronic obstructive pulmonary disease, and/or asthma. The IG (n = 204) received the psychoeducational intervention (12 weekly sessions of 90 min), and the CG (n = 176) had standard care. The patients were evaluated at baseline, and at 4 and 12 months. The main outcome measures were clinical remission of depressive symptoms (BDI-II ≤ 13) and therapeutic response (reduction of depressive symptoms by 50%). Remission was not significant at four months. At 12 months it was 53.9% in the IG and 41.5% in the CG. (OR = 0.61, 95% CI, 0.49–0.76). At 4 months the response in the IG (OR = 0.59, 95% CI, 0.44–0.78) was significant, but not at 12 months. The psychoeducational group intervention led by PC nurses for individuals with depression and physical comorbidity has been shown to be effective for remission at long-term and for therapeutic response at short-term.

scholarly journals The innate immune function of airway epithelial cells in inflammatory lung disease

2015 ◽  
Vol 45 (4) ◽  
pp. 1150-1162 ◽  
Author(s):  
Pieter S. Hiemstra ◽  
Paul B. McCray ◽  
Robert Bals
Keyword(s):  
Immune Responses ◽  
Airway Epithelium ◽  
Cell Function ◽  
Developmental Regulation ◽  
Airway Epithelial Cells ◽  
Chronic Obstructive ◽  
Airway Epithelial ◽  
Tissue Remodelling ◽  
Wide Range ◽  
Differentiation Pathways

The airway epithelium is now considered to be central to the orchestration of pulmonary inflammatory and immune responses, and is also key to tissue remodelling. It acts as the first barrier in the defence against a wide range of inhaled challenges, and is critically involved in the regulation of both innate and adaptive immune responses to these challenges. Recent progress in our understanding of the developmental regulation of this tissue, the differentiation pathways, recognition of pathogens and antimicrobial responses is now exploited to help understand how epithelial cell function and dysfunction contributes to the pathogenesis of a variety of inflammatory lung diseases. Herein, advances in our knowledge of the biology of airway epithelium, as well as its role and (dys)function in asthma, chronic obstructive pulmonary fibrosis and cystic fibrosis will be discussed.

The Effect of Telerehabilitation on Quality of Life, Exercise Capacity, and Spirometry Indexes in Patients with Chronic Obstructive Pulmonary Disease in Masih Daneshvari Hospital

2021 ◽  
Author(s):  
Somayeh Ghadimi ◽  
Atefeh Fakharian ◽  
Mohsen Abedi ◽  
Reyhaneh Zahiri ◽  
Mahsan Norouz Afjeh ◽  
...  
Keyword(s):  
Quality Of Life ◽  
Chronic Obstructive Pulmonary Disease ◽  
Pulmonary Disease ◽  
Control Group ◽  
Chronic Obstructive ◽  
Obstructive Pulmonary Disease ◽  
Copd Patients ◽  
And Control

Background: Chronic Obstructive Pulmonary Disease (COPD) leads to limited activity and reduced quality of life. Treatment of this disease is a long-term process that requires the cooperation of patients in monitoring and treatment. Methods: In the present study which was conducted from April 2019 to March 2021 in Masih Daneshvari Hospital, Tehran, Iran, 75 patients were randomly divided into telerehabilitation and control groups. Patients in the control group received pulmonary rehabilitation including respiratory, isometric, and aerobic exercises for 8 weeks, three times per week. In the second group, patients were given a lung rehabilitation booklet and asked to repeat the exercises three times a week for four weeks according to a specific schedule. In addition, patients installed Behzee care application on the mobile phone that recorded various indicators such as heart rate, SpO2, dyspnea, fatigue, and daily activities. This application reminded the patient of the program every day and at a specific time. Finally, the patients’ conditions were compared in the two groups after 8 weeks using CAT and mMRC questionnaires and 6-Minute Walk (6MW) exercise indices as well as spirometry tests. Results: In all four indicators (6MW, CAT,  and mMRC questionnaires as well as spirometry), patients showed improvement after rehabilitation (p<0.001). This improvement was significantly higher in the telemedicine group compared to the other group (p<0.01). Conclusion: The use of telerehabilitation in COPD patients is effective in improving spirometry indices, quality of life, as well as activity and sports indices.

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