scholarly journals Hsp10 nuclear localization and changes in lung cells response to cigarette smoke suggest novel roles for this chaperonin

Open Biology ◽  
2014 ◽  
Vol 4 (10) ◽  
pp. 140125 ◽  
Author(s):  
Simona Corrao ◽  
Rita Anzalone ◽  
Melania Lo Iacono ◽  
Tiziana Corsello ◽  
Antonino Di Stefano ◽  
...  
Keyword(s):  
Cigarette Smoke ◽  
Chronic Obstructive ◽  
Lung Cells ◽  
Obstructive Pulmonary Disease ◽  
Bronchial Epithelial ◽  
Pathological Conditions ◽  
Before And After ◽  
Nuclear Levels ◽  
Qualitative Changes

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) and lung fibroblast (HFL-1) cells, in vitro , showed Hsp10 in the nucleus, before and after CSE exposure; (iii) CSE stimulation did not increase the levels of Hsp10 but did elicit qualitative changes as indicated by molecular weight and isoelectric point shifts; and (iv) Hsp10 nuclear levels increased after CSE stimulation in HFL-1, indicating cytosol to nucleus migration, and although Hsp10 did not bind DNA, it bound a DNA-associated protein.

scholarly journals Loading of Beclomethasone in Liposomes and Hyalurosomes Improved with Mucin as Effective Approach to Counteract the Oxidative Stress Generated by Cigarette Smoke Extract

Nanomaterials ◽  
2021 ◽  
Vol 11 (4) ◽  
pp. 850
Author(s):  
Maria Letizia Manca ◽  
Maria Ferraro ◽  
Elisabetta Pace ◽  
Serena Di Vincenzo ◽  
Donatella Valenti ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Cigarette Smoke ◽  
Room Temperature ◽  
Cigarette Smoke Extract ◽  
Chronic Obstructive ◽  
Obstructive Pulmonary Disease ◽  
Bronchial Epithelial ◽  
Promising Tool ◽  
Next Generation Impactor

In this work beclomethasone dipropionate was loaded into liposomes and hyalurosomes modified with mucin to improve the ability of the payload to counteract the oxidative stress and involved damages caused by cigarette smoke in the airway. The vesicles were prepared by dispersing all components in the appropriate vehicle and sonicating them, thus avoiding the use of organic solvents. Unilamellar and bilamellar vesicles small in size (~117 nm), homogeneously dispersed (polydispersity index lower than 0.22) and negatively charged (~−11 mV), were obtained. Moreover, these vesicle dispersions were stable for five months at room temperature (~25 °C). In vitro studies performed using the Next Generation Impactor confirmed the suitability of the formulations to be nebulized as they were capable of reaching the last stages of the impactor that mimic the deeper airways, thus improving the deposition of beclomethasone in the target site. Further, biocompatibility studies performed by using 16HBE bronchial epithelial cells confirmed the high biocompatibility and safety of all the vesicles. Among the tested formulations, only mucin-hyalurosomes were capable of effectively counteracting the production of reactive oxygen species (ROS) induced by cigarette smoke extract, suggesting that this formulation may represent a promising tool to reduce the damaging effects of cigarette smoke in the lung tissues, thus reducing the pathogenesis of cigarette smoke-associated diseases such as chronic obstructive pulmonary disease, emphysema, and cancer.

Role of the IL-33/ST2 axis in cigarette smoke-induced airways remodelling in chronic obstructive pulmonary disease

Thorax ◽  
2021 ◽  
pp. thoraxjnl-2020-214712
Author(s):  
Qiong Huang ◽  
Chen Duo Li ◽  
Yi Ran Yang ◽  
Xiao Feng Qin ◽  
Jing Jing Wang ◽  
...  
Keyword(s):  
Cigarette Smoke ◽  
Lavage Fluid ◽  
Chronic Obstructive ◽  
Tissue Remodelling ◽  
Tissue Samples ◽  
Obstructive Pulmonary Disease ◽  
Interleukin 33 ◽  
Multiple Organs

BackgroundEfficient therapy and potential prophylaxis are confounded by current ignorance of the pathogenesis of airway remodelling and blockade in COPD.ObjectiveTo explore the role of the IL-33/ST2 axis in cigarette smoke (CS) exposure-induced airways remodelling.MethodsC57BL/6, BALB/c and IL-1RL1-/- mice exposed to CS were used to establish an animal surrogate of COPD (air-exposed=5~8, CS-exposed=6~12). Hallmarks of remodelling were measured in mice. Cigarette smoke extract (CSE)-induced proliferation and protein production in vitro by fibroblasts in the presence of anti-interleukin-33 (anti-IL-33) or hST2 antibodies were measured. Expression of IL-33 and ST2 and other remodelling hallmarks were measured, respectively, in bronchoalveolar lavage fluid (BALF) (controls=20, COPD=20), serum (controls=59, COPD=90) and lung tissue sections (controls=11, COPD=7) from patients with COPD and controls.ResultsWild-type mice exposed to CS elevated expression of hallmarks of tissue remodelling in the lungs and also in the heart, spleen and kidneys, which were significantly abrogated in the IL-1RL1-/- mice. Fibroblasts exposed to CSE, compared with control, exhibited early cellular translocation of IL-33, accompanied by proliferation and elevated protein synthesis, all inhabitable by blockade of IL-33/ST2 signalling. Expression of IL-33 and ST2 and hallmarks of tissue remodelling were significantly and proportionally elevated in BALF, serum and tissue samples from patients with COPD.ConclusionsExposure to CS induces remodelling changes in multiple organs. The data support the hypothesis that CS-induced lung collagen deposition is at least partly a result of CS-induced IL-33 translocation and release from local fibroblasts.

scholarly journals Increased IgA production by B-cells in COPDvialung epithelial interleukin-6 and TACI pathways

2014 ◽  
Vol 45 (4) ◽  
pp. 980-993 ◽  
Author(s):  
Maha Zohra Ladjemi ◽  
Marylène Lecocq ◽  
Birgit Weynand ◽  
Holly Bowen ◽  
Hannah J. Gould ◽  
...  
Keyword(s):  
B Cells ◽  
B Cell ◽  
Cigarette Smoke ◽  
Lung Tissue ◽  
Plasma Cells ◽  
Bronchial Epithelium ◽  
Chronic Obstructive ◽  
Promoting Effect ◽  
Obstructive Pulmonary Disease

Despite their relevance to mucosal defense, production of IgA and the function of lung B-cells remain unknown in chronic obstructive pulmonary disease (COPD).We assessed IgA synthesis in the lungs of COPD (n=28) and control (n=21) patients, and regulation of B-cells co-cultured within vitro-reconstituted airway epithelium.In COPD lung tissue, synthesis of IgA1 was increased, which led to its accumulation in subepithelial areas.In vitro, the COPD bronchial epithelium imprinted normal human B-cells for increased production of IgA (mainly IgA1) and maturation into CD38+plasma cells. These effects were associated with upregulation of TACI (transmembrane activator and CAML interactor) and were observed under resting conditions, while being partly inhibited upon stimulation with cigarette smoke extract. Interleukin (IL)-6 and BAFF (B-cell activating factor)/APRIL (a proliferation-inducing ligand) were upregulated in the COPD epithelium and lung tissue, respectively; the IgA-promoting effect of the COPD bronchial epithelium was inhibited by targeting IL-6 and, to a lower extent, by blocking TACI.These data show that in COPD, the bronchial epithelium imprints B-cells with signals promoting maturation into IgA-producing plasma cells through the action of two epithelial/B-cell axes, namely the IL-6/IL-6 receptor and BAFF-APRIL/TACI pathways, while cigarette smoke partly counteracts this IgA-promoting effect.

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.

scholarly journals Endothelial Progenitor Cells as Pathogenetic and Diagnostic Factors, and Potential Targets for GLP-1 in Combination with Metabolic Syndrome and Chronic Obstructive Pulmonary Disease

2019 ◽  
Vol 20 (5) ◽  
pp. 1105 ◽  
Author(s):  
Evgenii Skurikhin ◽  
Olga Pershina ◽  
Angelina Pakhomova ◽  
Edgar Pan ◽  
Vyacheslav Krupin ◽  
...  
Keyword(s):  
Chronic Obstructive Pulmonary Disease ◽  
Metabolic Syndrome ◽  
Endothelial Cells ◽  
Progenitor Cells ◽  
Pulmonary Disease ◽  
Endothelial Progenitor Cells ◽  
Cigarette Smoke ◽  
Chronic Obstructive ◽  
Obstructive Pulmonary Disease

In clinical practice, there are patients with a combination of metabolic syndrome (MS) and chronic obstructive pulmonary disease (COPD). The pathological mechanisms linking MS and COPD are largely unknown. It remains unclear whether the effect of MS (possible obesity) has a major impact on the progression of COPD. This complicates the development of effective approaches for the treatment of patients with a diagnosis of MS and COPD. Experiments were performed on female C57BL/6 mice. Introduction of monosodium glutamate and extract of cigarette smoke was modeled to simulate the combined pathology of lipid disorders and emphysema. Biological effects of glucagon-like peptide 1 (GLP-1) and GLP-1 on endothelial progenitor cells (EPC) in vitro and in vivo were evaluated. Histological, immunohistochemical methods, biochemical methods, cytometric analysis of markers identifying EPC were used in the study. The CD31+ endothelial cells in vitro evaluation was produced by Flow Cytometry and Image Processing of each well with a Cytation™ 3. GLP-1 reduces the area of emphysema and increases the number of CD31+ endothelial cells in the lungs of mice in conditions of dyslipidemia and damage to alveolar tissue of cigarette smoke extract. The regenerative effects of GLP-1 are caused by a decrease in inflammation, a positive effect on lipid metabolism and glucose metabolism. EPC are proposed as pathogenetic and diagnostic markers of endothelial disorders in combination of MS with COPD. Based on GLP-1, it is proposed to create a drug to stimulate the regeneration of endothelium damaged in MS and COPD.

scholarly journals Dendritic cells induce Tc1 cell differentiation via the CD40/CD40L pathway in mice after exposure to cigarette smoke

2016 ◽  
Vol 311 (3) ◽  
pp. L581-L589 ◽  
Author(s):  
Liang-Jian Kuang ◽  
Ting-Ting Deng ◽  
Qin Wang ◽  
Shi-Lin Qiu ◽  
Yi Liang ◽  
...  
Keyword(s):  
Dendritic Cells ◽  
Cell Differentiation ◽  
Cigarette Smoke ◽  
Lung Damage ◽  
Chronic Obstructive ◽  
Wild Type ◽  
Control Groups ◽  
Obstructive Pulmonary Disease

Dendritic cells and CD8+ T cells participate in the pathology of chronic obstructive pulmonary disease, including emphysema, but little is known of the involvement of the CD40/CD40L pathway. We investigated the role of the CD40/CD40L pathway in Tc1 cell differentiation induced by dendritic cells in a mouse model of emphysema, and in vitro. C57BL/6J wild-type and CD40−/− mice were exposed to cigarette smoke (CS) or not (control), for 24 wk. In vitro experiments involved wild-type and CD40−/− dendritic cells treated with CS extract (CSE) or not. Compared with the control groups, the CS mice (both wild type and CD40−/−) had a greater percentage of lung dendritic cells and higher levels of major histocompatability complex (MHC) class I molecules and costimulatory molecules CD40 and CD80. Relative to the CS CD40−/− mice, the CS wild type showed greater signs of lung damage and Tc1 cell differentiation. In vitro, the CSE-treated wild-type cells evidenced more cytokine release (IL-12/p70) and Tc1 cell differentiation than did the CSE-treated CD40−/− cells. Exposure to cigarette smoke increases the percentage of lung dendritic cells and promotes Tc1 cell differentiation via the CD40/CD40L pathway. Blocking the CD40/CD40L pathway may suppress development of emphysema in mice exposed to cigarette smoke.

scholarly journals Sappanone A inhibits oxidative stress, inflammation and apoptosis in cigarette smoke-induced human bronchial epithelial cells through regulating Nrf2/HO-1 and TLR4/NF-κB signaling pathways

2020 ◽  
Author(s):  
Yan Zhang ◽  
Shanshan Wang ◽  
Hongli Li ◽  
Xia Xu
Keyword(s):  
Oxidative Stress ◽  
Epithelial Cells ◽  
Signaling Pathways ◽  
Signaling Pathway ◽  
Cigarette Smoke ◽  
Bronchial Epithelial Cells ◽  
Chronic Obstructive ◽  
Human Bronchial Epithelial Cells ◽  
Bronchial Epithelial

Abstract Chronic obstructive pulmonary disease (COPD) is a common respiratory disease associated with inflammation and oxidative stress. Sappanone A (SA) is a homoisoflavanone that has been proven to have anti-inflammatory and anti-oxidant effects. However, the role of SA in COPD remains unclear. Thus, the present study was aimed to evaluate the beneficial effect of SA on COPD in vitro. The human bronchial epithelial cells were exposed to 5% cigarette smoke extracts (CSE) to induce an in vitro model of COPD. Our results showed that SA treatment significantly attenuated the CSE-caused induction of ROS and reduction of SOD and GPx activities in 16HBE cells. In addition, SA inhibited the production of inflammatory cytokines IL-6, IFN-γ, and TNF-α in CSE-stimulated 16HBE cells. Moreover, the CSE-stimulated cell apoptosis of 16HBE cells were abrogated by SA. Furthermore, we observed that SA treatment greatly promoted the activation of Nrf2/HO-1 signaling pathway, as well as inhibited the activation of TLR4/NF-κB signaling pathway in CSE-stimulated 16HBE cells. Subsequent rescue assay revealed that the protective effects of SA on CSE-stimulated 16HBE cells were reversed by Nrf2 knockdown or TLR4 overexpression. Taken together, these findings demonstrated that SA inhibits oxidative stress, inflammation and apoptosis in CSE-induced human bronchial epithelial cells through regulating Nrf2/HO-1 and TLR4/NF-κB signaling pathways.

scholarly journals Cigarette smoke extract stimulates bronchial epithelial cells to undergo a SUMOylation turnover

2020 ◽  
Vol 20 (1) ◽  
Author(s):  
Haifeng Zhou ◽  
Lei Zhang ◽  
Yang Li ◽  
Guorao Wu ◽  
He Zhu ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Epithelial Cells ◽  
Cigarette Smoke ◽  
Posttranslational Modifications ◽  
Bronchial Epithelial Cells ◽  
Chronic Obstructive ◽  
Cytochrome P450 1A1 ◽  
Obstructive Pulmonary Disease ◽  
Bronchial Epithelial ◽  
Bioinformatic Tools

Abstract Background Chronic obstructive pulmonary disease (COPD) characterized by the airway and lung inflammation, is a leading cause of morbidity and mortality worldwide, especially among smokers over 40 years of age and individuals exposed to biomass smoke. Although the detailed mechanisms of this disease remain elusive, there is feasible evidence that protein posttranslational modifications (PTMs) may play a role in its pathoetiology. We thus conducted studies to dissect the effect of cigarette smoke extracts (CSE) on the change of SUMOylated substrates in human bronchial epithelial cells (HBEs). Methods Samples were collected in HBEs with or without 24 h of CSE insult and then subjected to Western-blot and LC-MS/MS analysis. Subsequently, bioinformatic tools were used to analyze the data. The effect of SUMOylation on cytochrome P450 1A1 (CYP1A1) was evaluated by flow cytometry. Results It was noted that CSE stimulated HBEs to undergo a SUMOylation turnover as evidenced by the changes of SUMOylated substrates and SUMOylation levels for a particular substrate. The SUMOylated proteins are relevant to the regulation of biological processes, molecular function and cellular components. Particularly, CSE stimulated a significant increase of SUMOylated CYP1A1, a critical enzyme involved in the induction of oxidative stress. Conclusions Our data provide a protein SUMOylation profile for better understanding of the mechanisms underlying COPD and support that smoking induces oxidative stress in HBEs, which may predispose to the development of COPD in clinical settings.

scholarly journals Will chronic e-cigarette use cause lung disease?

2015 ◽  
Vol 309 (12) ◽  
pp. L1398-L1409 ◽  
Author(s):  
Temperance R. Rowell ◽  
Robert Tarran
Keyword(s):  
Tobacco Smoking ◽  
Chronic Obstructive ◽  
Lung Cells ◽  
Cigarette Use ◽  
Obstructive Pulmonary Disease ◽  
Isolated Lung ◽  
Mammalian Lung ◽  
Never Smokers ◽  
New Generation

Chronic tobacco smoking is a major cause of preventable morbidity and mortality worldwide. In the lung, tobacco smoking increases the risk of lung cancer, and also causes chronic obstructive pulmonary disease (COPD), which encompasses both emphysema and chronic bronchitis. E-cigarettes (E-Cigs), or electronic nicotine delivery systems, were developed over a decade ago and are designed to deliver nicotine without combusting tobacco. Although tobacco smoking has declined since the 1950s, E-Cig usage has increased, attracting both former tobacco smokers and never smokers. E-Cig liquids (e-liquids) contain nicotine in a glycerol/propylene glycol vehicle with flavorings, which are vaporized and inhaled. To date, neither E-Cig devices, nor e-liquids, are regulated by the Food and Drug Administration (FDA). The FDA has proposed a deeming rule, which aims to initiate legislation to regulate E-Cigs, but the timeline to take effect is uncertain. Proponents of E-Cigs say that they are safe and should not be regulated. Opposition is varied, with some opponents proposing that E-Cig usage will introduce a new generation to nicotine addiction, reversing the decline seen with tobacco smoking, or that E-Cigs generally may not be safe and will trigger diseases like tobacco. In this review, we shall discuss what is known about the effects of E-Cigs on the mammalian lung and isolated lung cells in vitro. We hope that collating this data will help illustrate gaps in the knowledge of this burgeoning field, directing researchers toward answering whether or not E-Cigs are capable of causing disease.

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