Correction: Ergosterol attenuates cigarette smoke extract-induced COPD by modulating inflammation, oxidative stress and apoptosis in vitro and in vivo

Abstract Cigarette smoke (CS) is the major cause of chronic obstructive pulmonary disease (COPD). CS heightens inflammation, oxidative stress and apoptosis. Ergosterol is the main bioactive ingredient in Cordyceps sinensis (C. sinensis), a traditional medicinal herb for various diseases. The objective of this work was to investigate the effects of ergosterol on anti-inflammatory and antioxidative stress as well as anti-apoptosis in a cigarette smoke extract (CSE)-induced COPD model both in vitro and in vivo. Our results demonstrate that CSE induced inflammatory and oxidative stress and apoptosis with the involvement of the Bcl-2 family proteins via the nuclear factor kappa B (NF-κB)/p65 pathway in both 16HBE cells and Balb/c mice. CSE induced epithelial cell death and increased the expression of nitric oxide (NO), interleukin-6 (IL-6), tumor necrosis factor α (TNF-α), malondialdehyde (MAD) and the apoptosis-related proteins cleaved caspase 3/7/9 and cleaved-poly-(ADP)-ribose polymerase (PARP) both in vitro and in vivo, whereas decreased the levels of superoxide dismutase (SOD) and catalase (CAT). Treatment of 16HBE cells and Balb/c mice with ergosterol inhibited CSE-induced inflammatory and oxidative stress and apoptosis by inhibiting the activation of NF-κB/p65. Ergosterol suppressed apoptosis by inhibiting the expression of the apoptosis-related proteins both in vitro and in vivo. Moreover, the usage of QNZ (an inhibitor of NF-κB) also partly demonstrated that NF-κB/p65 pathway was involved in the ergosterol protective progress. These results show that ergosterol suppressed COPD inflammatory and oxidative stress and apoptosis through the NF-κB/p65 pathway, suggesting that ergosterol may be partially responsible for the therapeutic effects of cultured C. sinensis on COPD patients.

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Paeonol Attenuates Cigarette Smoke-Induced Lung Inflammation by Inhibiting ROS-Sensitive Inflammatory Signaling

Mediators of Inflammation ◽

10.1155/2014/651890 ◽

2014 ◽

Vol 2014 ◽

pp. 1-13 ◽

Cited By ~ 37

Author(s):

Meng-Han Liu ◽

An-Hsuan Lin ◽

Hung-Fu Lee ◽

Hsin-Kuo Ko ◽

Tzong-Shyuan Lee ◽

...

Keyword(s):

Oxidative Stress ◽

Cigarette Smoke ◽

Lung Inflammation ◽

Chinese Herb ◽

Inflammatory Infiltration ◽

Beneficial Effects ◽

Antioxidant Function ◽

Mitogen Activated Protein

Cigarette smoking causes persistent lung inflammation that is mainly regulated by redox-sensitive pathways. We have previously reported that cigarette smoke (CS) activates reactive oxygen species- (ROS-) sensitive mitogen-activated protein kinases (MAPKs)/nuclear factor-κB (NF-κB) signaling leading to induction of lung inflammation. Paeonol, the main phenolic compound present in the Chinese herbPaeonia suffruticosa, has antioxidant and anti-inflammatory properties. However, whether paeonol has similar beneficial effects against CS-induced lung inflammation remains unclear. Using a murine model, we showed that chronic CS exposure for 4 weeks caused pulmonary inflammatory infiltration, increased lung vascular permeability, elevated lung levels of chemokines, cytokines, and 4-hydroxynonenal (an oxidative stress biomarker), and induced lung inflammation; all of these CS-induced events were suppressed by chronic treatment with paeonol. Using human bronchial epithelial cells (HBECs), we demonstrated that cigarette smoke extract (CSE) sequentially increased extracellular and intracellular levels of ROS, activated the MAPKs/NF-κB signaling, and induced interleukin-8 (IL-8); all these CSE-induced events were inhibited by paeonol pretreatment. Our findings suggest a novel role for paeonol in alleviating the oxidative stress and lung inflammation induced by chronic CS exposurein vivoand in suppressing CSE-induced IL-8in vitrovia its antioxidant function and an inhibition of the MAPKs/NF-κB signaling.

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

Nanomaterials ◽

10.3390/nano11040850 ◽

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.

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Cigarette smoke extract combined with lipopolysaccharide reduces OCTN1/2 expression in human alveolar epithelial cells in vitro and rat lung in vivo under inflammatory conditions

International Immunopharmacology ◽

10.1016/j.intimp.2020.106812 ◽

2020 ◽

Vol 87 ◽

pp. 106812 ◽

Cited By ~ 1

Author(s):

Chuanzong Qi ◽

Jian Zhou ◽

Zihao Wang ◽

Xin Fang ◽

Dalang Li ◽

...

Keyword(s):

Epithelial Cells ◽

Cigarette Smoke ◽

Cigarette Smoke Extract ◽

Alveolar Epithelial Cells ◽

Rat Lung ◽

Alveolar Epithelial ◽

Inflammatory Conditions ◽

Human Alveolar Epithelial Cells

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Transcriptional Response of Mycobacterium tuberculosis to Cigarette Smoke Condensate

Frontiers in Microbiology ◽

10.3389/fmicb.2021.744800 ◽

2021 ◽

Vol 12 ◽

Author(s):

Danicke Willemse ◽

Chivonne Moodley ◽

Smriti Mehra ◽

Deepak Kaushal

Keyword(s):

Oxidative Stress ◽

Mycobacterium Tuberculosis ◽

Cigarette Smoke ◽

Mutation Frequency ◽

Transcriptional Response ◽

Cigarette Smoke Condensate ◽

Stress Survival ◽

The Impact

Smoking is known to be an added risk factor for tuberculosis (TB), with nearly a quarter of the TB cases attributed to cigarette smokers in the 22 countries with the highest TB burden. Many studies have indicated a link between risk of active TB and cigarette smoke. Smoking is also known to significantly decrease TB cure and treatment completion rate and increase mortality rates. Cigarette smoke contains thousands of volatile compounds including carcinogens, toxins, reactive solids, and oxidants in both particulate and gaseous phase. Yet, to date, limited studies have analyzed the impact of cigarette smoke components on Mycobacterium tuberculosis (Mtb), the causative agent of TB. Here we report the impact of cigarette smoke condensate (CSC) on survival, mutation frequency, and gene expression of Mtb in vitro. We show that exposure of virulent Mtb to cigarette smoke increases the mutation frequency of the pathogen and strongly induces the expression of the regulon controlled by SigH—a global transcriptional regulator of oxidative stress. SigH has previously been shown to be required for Mtb to respond to oxidative stress, survival, and granuloma formation in vivo. A high-SigH expression phenotype is known to be associated with greater virulence of Mtb. In patients with pulmonary TB who smoke, these changes may therefore play an important, yet unexplored, role in the treatment efficacy by potentially enhancing the virulence of tubercle bacilli.

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Cigarette smoke causes lung vascular barrier dysfunction via oxidative stress-mediated inhibition of RhoA and focal adhesion kinase

AJP Lung Cellular and Molecular Physiology ◽

10.1152/ajplung.00178.2011 ◽

2011 ◽

Vol 301 (6) ◽

pp. L847-L857 ◽

Cited By ~ 42

Author(s):

Qing Lu ◽

Pavlo Sakhatskyy ◽

Katie Grinnell ◽

Julie Newton ◽

Melanie Ortiz ◽

...

Keyword(s):

Oxidative Stress ◽

Focal Adhesion Kinase ◽

Cigarette Smoke ◽

Focal Adhesion ◽

Underlying Mechanism ◽

Endothelial Barrier ◽

Barrier Dysfunction ◽

Endothelial Barrier Dysfunction

Cigarette smoke (CS) is a major cause of chronic lung and cardiovascular diseases. Recent studies indicate that tobacco use is also a risk factor for acute lung injury (ALI) associated with blunt trauma. Increased endothelial cell (EC) permeability is a hallmark of ALI. CS increases EC permeability in vitro and in vivo; however, the underlying mechanism is not well understood. In this study, we found that only 6 h of exposure to CS impaired endothelial barrier function in vivo, an effect associated with increased oxidative stress in the lungs and attenuated by the antioxidant N-acetylcysteine (NAC). CS also exacerbated lipopolysaccharide (LPS)-induced increase in vascular permeability in vivo. Similar additive effects were also seen in cultured lung EC exposed to cigarette smoke extract (CSE) and LPS. We further demonstrated that CSE caused disruption of focal adhesion complexes (FAC), F-actin fibers, and adherens junctions (AJ) and decreased activities of RhoA and focal adhesion kinase (FAK) in cultured lung EC. CSE-induced inhibition of RhoA and FAK, endothelial barrier dysfunction, and disassembly of FAC, F-actin, and AJ were prevented by NAC. In addition, the deleterious effects of CSE on FAC, F-actin fibers, and AJ were blunted by overexpression of constitutively active RhoA and of FAK. Our data indicate that CS causes endothelial barrier dysfunction via oxidative stress-mediated inhibition of RhoA and FAK.

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Glutathione peroxidase-1 protects against cigarette smoke-induced lung inflammation in mice

AJP Lung Cellular and Molecular Physiology ◽

10.1152/ajplung.00038.2010 ◽

2010 ◽

Vol 299 (3) ◽

pp. L425-L433 ◽

Cited By ~ 51

Author(s):

Chi Duong ◽

Huei Jiunn Seow ◽

Steven Bozinovski ◽

Peter J. Crack ◽

Gary P. Anderson ◽

...

Keyword(s):

Oxidative Stress ◽

Glutathione Peroxidase ◽

Cigarette Smoke ◽

Lung Inflammation ◽

Protein Denaturation ◽

Lung Damage ◽

Glutathione Peroxidase 1 ◽

Neutrophil Chemotactic Factor

Reactive oxygen species (ROS) produced from cigarette smoke cause oxidative lung damage including protein denaturation, lipid peroxidation, and DNA damage. Glutathione peroxidase-1 (gpx-1) is a detoxifying enzyme that may protect lungs from such damage. The aim of this study was to determine whether gpx-1 protects the lung against oxidative stress-induced lung inflammation in vivo. Male wild-type (WT) or gpx-1−/− mice were exposed to cigarette smoke generated from nine cigarettes per day for 4 days to induce oxidative stress and lung inflammation. The effect of the gpx mimetic ebselen on cigarette smoke-induced lung inflammation was evaluated when given prophylactically and therapeutically, i.e., during established inflammation. Mice were killed, and the lungs were lavaged with PBS and then harvested for genomic and proteomic analysis. Gpx-1−/− mice exposed to cigarette smoke had enhanced BALF neutrophils, macrophages, proteolytic burden, whole lung IL-17A, and MIP1α mRNA compared with WT mice. The gpx mimetic ebselen (10 and 100 μM) inhibited cigarette smoke extract-induced oxidation of MH-S cells in vitro and inhibited cigarette smoke-induced increases in BALF macrophages, neutrophils, proteolytic burden, and macrophage and neutrophil chemotactic factor gene expression when administered prophylactically. In addition, ebselen inhibited established BALF inflammation when administered therapeutically. These data show that gpx-1 protects against cigarette smoke-induced lung inflammation, and agents that mimic the actions of gpx-1 may have therapeutic utility in inflammatory lung diseases where cigarette smoke plays a role.

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