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

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

Clinical Science ◽

10.1042/cs20190331 ◽

2019 ◽

Vol 133 (13) ◽

pp. 1523-1536 ◽

Cited By ~ 8

Author(s):

Xiao Sun ◽

Xiuli Feng ◽

Dandan Zheng ◽

Ang Li ◽

Chunyan Li ◽

...

Keyword(s):

Oxidative Stress ◽

Cigarette Smoke ◽

Cigarette Smoke Extract ◽

Cordyceps Sinensis ◽

Chronic Obstructive ◽

Therapeutic Effects ◽

Related Proteins ◽

And Oxidative Stress

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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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

10.21203/rs.3.rs-36518/v1 ◽

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.

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

BMC Pulmonary Medicine ◽

10.1186/s12890-020-01300-w ◽

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.

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

Open Biology ◽

10.1098/rsob.140125 ◽

2014 ◽

Vol 4 (10) ◽

pp. 140125 ◽

Cited By ~ 10

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.

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Loss of IL-33 enhances elastase-induced and cigarette smoke extract-induced emphysema in mice

Respiratory Research ◽

10.1186/s12931-021-01705-z ◽

2021 ◽

Vol 22 (1) ◽

Author(s):

Daisuke Morichika ◽

Akihiko Taniguchi ◽

Naohiro Oda ◽

Utako Fujii ◽

Satoru Senoo ◽

...

Keyword(s):

Cigarette Smoke ◽

Intratracheal Instillation ◽

Inflammatory Cells ◽

Cigarette Smoke Extract ◽

Lymphoid Cells ◽

Chronic Obstructive ◽

Porcine Pancreas ◽

Obstructive Pulmonary Disease ◽

Quantitative Morphometry ◽

Cytokines And Chemokines

Abstract Background IL-33, which is known to induce type 2 immune responses via group 2 innate lymphoid cells, has been reported to contribute to neutrophilic airway inflammation in chronic obstructive pulmonary disease. However, its role in the pathogenesis of emphysema remains unclear. Methods We determined the role of interleukin (IL)-33 in the development of emphysema using porcine pancreas elastase (PPE) and cigarette smoke extract (CSE) in mice. First, IL-33−/− mice and wild-type (WT) mice were given PPE intratracheally. The numbers of inflammatory cells, and the levels of cytokines and chemokines in the bronchoalveolar lavage (BAL) fluid and lung homogenates, were analyzed; quantitative morphometry of lung sections was also performed. Second, mice received CSE by intratracheal instillation. Quantitative morphometry of lung sections was then performed again. Results Intratracheal instillation of PPE induced emphysematous changes and increased IL-33 levels in the lungs. Compared to WT mice, IL-33−/− mice showed significantly greater PPE-induced emphysematous changes. No differences were observed between IL-33−/− and WT mice in the numbers of macrophages or neutrophils in BAL fluid. The levels of hepatocyte growth factor were lower in the BAL fluid of PPE-treated IL-33−/− mice than WT mice. IL-33−/− mice also showed significantly greater emphysematous changes in the lungs, compared to WT mice, following intratracheal instillation of CSE. Conclusion These observations suggest that loss of IL-33 promotes the development of emphysema and may be potentially harmful to patients with COPD.

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Pirfenidone mediates cigarette smoke extract induced inflammation and oxidative stress in vitro and in vivo

International Immunopharmacology ◽

10.1016/j.intimp.2021.107593 ◽

2021 ◽

Vol 96 ◽

pp. 107593

Author(s):

Yiming Ma ◽

Lijuan Luo ◽

Xiangming Liu ◽

Herui Li ◽

Zihang Zeng ◽

...

Keyword(s):

Oxidative Stress ◽

Cigarette Smoke ◽

Cigarette Smoke Extract ◽

And Oxidative Stress

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Exposure to the gut microbiota from cigarette smoke-exposed mice exacerbates cigarette smoke extract-induced inflammation in zebrafish larvae

10.1101/2021.09.20.461170 ◽

2021 ◽

Author(s):

Simone Morris ◽

Kathryn Wright ◽

Vamshikrishna Malyla ◽

Warwick J Britton ◽

Philip M Hansbro ◽

...

Keyword(s):

Cigarette Smoking ◽

Gut Microbiota ◽

Cigarette Smoke ◽

Cigarette Smoke Extract ◽

Chronic Obstructive ◽

Obstructive Pulmonary Disease ◽

Zebrafish Larvae ◽

Modifying Factors ◽

Physiological Processes ◽

Inflammatory Phenotype

AbstractCigarette smoke (CS)-induced inflammation leads to a range of diseases including chronic obstructive pulmonary disease and cancer. Environmental factors including gut microbiota make up are major modifying factors that determine the severity of cigarette smoke-induced pathology. Adult zebrafish display increased inflammatory cytokine transcription when exposed to cigarette smoke extract (CSE) but incongruously do not produce a mucosal leukocytic inflammation phenotype. Zebrafish embryos and larvae have been used to model the effects of cigarette smoking on a range of physiological processes and offer an amenable platform for screening modifiers of cigarette smoke-induced pathologies. Here we exposed zebrafish larvae to CSE and showed that it was toxic and we characterised a CSE-induced leukocytic inflammatory phenotype with increased neutrophilic and macrophage responses. The CSE-induced phenotype was exacerbated by co-exposure to microbiota from the faeces of CS-exposed mice, but not control mice. Microbiota could be recovered from the gut of zebrafish and studied in isolation. This demonstrates the utility of the zebrafish-CSE exposure platform for identifying environmental modifiers of cigarette smoking-associated pathology and demonstrates that the CS-exposed mouse gut microbiota potentiates the inflammatory effects of CSE across host species.

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Erythromycin Suppresses the Cigarette Smoke Extract-Exposed Dendritic Cell-Mediated Polarization of CD4+ T Cells into Th17 Cells

Journal of Immunology Research ◽

10.1155/2020/1387952 ◽

2020 ◽

Vol 2020 ◽

pp. 1-9

Author(s):

Jifeng Liu ◽

Xiaoning Zhong ◽

Zhiyi He ◽

Jianquan Zhang ◽

Jing Bai ◽

...

Keyword(s):

T Cells ◽

Cigarette Smoke ◽

Th17 Cells ◽

Mixed Lymphocyte Reaction ◽

Mononuclear Cells ◽

Cigarette Smoke Extract ◽

Exposed Group ◽

Control Group ◽

Chronic Obstructive ◽

Obstructive Pulmonary Disease

Cigarette smoke is a major effector of chronic obstructive pulmonary disease (COPD), and Th17 cells and dendritic cells (DCs) involve in the pathogenesis of COPD. Previous studies have demonstrated the anti-inflammatory effects of macrolides. However, the effects of macrolides on the cigarette smoke extract- (CSE-) induced immune response are unclear. Accordingly, in this study, we evaluated the effects of erythromycin (EM) on CSE-exposed DCs polarizing naïve CD4+ T cells into Th17 cells. DCs were generated from bone marrow-derived mononuclear cells isolated from male BALB/c mice and divided into five groups: control DC group, CSE-exposed DC group, CD40-antibody-blocked CSE-exposed DC group, and EM-treated CSE-exposed DC group. The function of polarizing CD4+ T cells into Th17 cells induced by all four groups of DCs was assayed based on the mixed lymphocyte reaction (MLR) of naïve CD4+ T cells. CD40 expression in DCs in the CSE-exposed group increased significantly compared with that in the control group (P<0.05). The Th17 cells in the CSE-exposed DC/MLR group increased significantly compared with those in the control DC/MLR group (P<0.05). Moreover, Th17 cells in the CD40-blocked CSE-exposed DC/MLR group and EM-treated CSE-exposed DC/MLR group were reduced compared with those in the CSE-exposed DC/MLR group (P<0.05). Thus, these findings suggested that EM suppressed the CSE-exposed DC-mediated polarization of CD4+ T cells into Th17 cells and that this effect may be mediated through inhibition of the CD40/CD40L pathway.

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