Cigarette smoke-mediated inflammatory and oxidative responses are strain-dependent in mice

2008 ◽  
Vol 294 (6) ◽  
pp. L1174-L1186 ◽  
Author(s):  
Hongwei Yao ◽  
Indika Edirisinghe ◽  
Saravanan Rajendrasozhan ◽  
Se-Ran Yang ◽  
Samuel Caito ◽  
...  
Keyword(s):  
Cigarette Smoke ◽  
Mouse Models ◽  
Molecular Mechanisms ◽  
Mouse Strains ◽  
Chronic Obstructive ◽  
Susceptible Mouse ◽  
Obstructive Pulmonary Disease ◽  
Resistant Mouse ◽  
Strain Dependent ◽  
Oxidative Responses

A variety of mouse models have been used to study the pathogenesis of pulmonary emphysema/chronic obstructive pulmonary disease. The effect of cigarette smoke (CS) is believed to be strain dependent, because certain mouse strains are more susceptible or resistant to development of emphysema. However, the molecular basis of susceptibility of mouse strains to effects of CS is not known. We investigated the effect of CS on lungs of most of the commonly used mouse strains to study the molecular mechanism of susceptibility to effects of CS. C57BL/6J, A/J, AKR/J, CD-1, and 129SvJ mice were exposed to CS for 3 consecutive days, and various parameters of inflammatory and oxidative responses were assessed in lungs of these mice. We found that the C57BL/6J strain was highly susceptible, the A/J, AKR/J, and CD-1 strains were moderately susceptible, and the 129SvJ strain was resistant to lung inflammatory and oxidant responses to CS exposure. The mouse strain that was more susceptible to effects of CS showed augmented lung inflammatory cell influx, activation of NF-κB and p38 MAPK, and increased levels of matrix metalloproteinase-9 and NF-κB-dependent proinflammatory cytokines compared with resistant mouse strains. Similarly, decreased levels of glutathione were associated with increased levels of lipid peroxidation products in susceptible mouse strains compared with resistant strains. Hence, we identified the susceptible and resistant mouse strains on the basis of the pattern of inflammatory and oxidant responses. Identification of sensitive and resistant mouse strains could be useful for studying the molecular mechanisms of effects of CS on inflammation and pharmacological interventional studies in CS-exposure mouse models.

Chrysene accelerates the proceeding of chronic obstructive pulmonary disease with the aggravation of inflammation and apoptosis in cigarette smoke exposed mice

2020 ◽  
pp. 096032712097934
Author(s):  
Yuan Gao ◽  
Xinjia Zhou ◽  
Yan Zhou ◽  
Wei Zhang ◽  
Li Zhao
Keyword(s):  
Chronic Obstructive Pulmonary Disease ◽  
Pulmonary Disease ◽  
Cigarette Smoke ◽  
Molecular Mechanisms ◽  
Smooth Muscle Actin ◽  
Lavage Fluid ◽  
Living Environment ◽  
Chronic Obstructive ◽  
High Morbidity ◽  
Obstructive Pulmonary Disease

Chrysene, one of the basic polycyclic aromatic hydrocarbons (PAHs), has been reported to make damages to human health and living environment. Chronic obstructive pulmonary disease (COPD) is a progressive disorder with high morbidity and mortality. To investigate the role of chrysene in the development of COPD, male C57BL/6 mice were exposed to the cigarette smoke (CS) followed with the administration of chrysene. Morphological analyses indicated that chrysene caused earlier and severer pathological changes in CS-exposed mice. Besides, CS-exposed mice with chrysene treatment showed obvious collagen deposition, elevated α-smooth muscle actin (α-SMA) expression and reduced E-cadherin abundance at earlier stage, which suggested the acceleration and aggravation of pulmonary fibrosis. Moreover, quantification of leukocytes and pro-inflammatory cytokines in bronchoalveolar lavage fluid (BALF) and lung tissues implied that chrysene significantly exacerbated the proceeding of inflammation in CS-exposed mice. Furthermore, significantly increased apoptotic rates, augmented expressions of apoptotic related proteins and highly expressed TRPV1 were determined in CS-exposed mice with chrysene treatment, which indicated the association between COPD pathogenesis and TRPV1 channel. In summary, our findings elucidate that chrysene accelerates the development of COPD in a murine model with new molecular mechanisms.

scholarly journals Direct Effects of Cigarette Smoke in Pulmonary Arterial Cells alter Vascular Tone through Arterial Remodeling and Kv7.4 Channel Dysregulation

2019 ◽  
Author(s):  
J Sevilla-Montero ◽  
D Labrousse-Arias ◽  
C Fernández-Pérez ◽  
B Barreira ◽  
G Mondejar-Parreño ◽  
...  
Keyword(s):  
Cigarette Smoke ◽  
Molecular Mechanisms ◽  
Pulmonary Arteries ◽  
Pulmonary Vasculature ◽  
Chronic Obstructive ◽  
Proliferative Potential ◽  
Direct Effects ◽  
Obstructive Pulmonary Disease ◽  
Cell Contractility ◽  
Pulmonary Arterial

AbstractChronic obstructive pulmonary disease (COPD) is a widespread disease, with no curative therapies nowadays. Exposure to cigarette smoking is considered the chief leading cause of COPD. Current drugs therapies improve patient quality of life, however they do not revert the progression of the disease. Therefore, a deeper study of the cellular and molecular mechanisms that underlie this pathology is required to be able to carry out targeted and effective treatments. Although the effects of cigarette smoke in the progressive deterioration of the airway have been extensively studied in COPD patients, its effects on pulmonary vasculature have been unexplored, due to the classic conception that vascular damage is a consequence of alveolar hypoxia and loss of capillary bed. In this paper, we aimed to study the effects of cigarette smoke extract (CSE) in regulating pulmonary arterial cells phenotypic modulation, in particular the effects in fibroblasts (hPAFib) and smooth muscle cells (hPASMC), and in murine pulmonary arteries. Our results demonstrated that CSE exposure had direct effects on hPAFib and hPASMC, promoting a senescent phenotype that in turn contributed, through the secretion of inflammatory molecules, to increase the proliferative potential of non-exposed cells. CSE also increased total ROS levels in hPAFib and hPASMC, and upregulated NADPH oxidase subunits NOX1 and p22phox. Most importantly, CSE affected cell contractility and dysregulated the expression and activity of voltage-gated K+ channel Kv7.4. This contributed to limit vascular responses impairing vasoconstriction and endothelium-dependent and independent relaxation.

scholarly journals LncRNA Nqo1-AS1 Attenuates Cigarette Smoke-Induced Oxidative Stress by Upregulating its Natural Antisense Transcript Nqo1

2021 ◽  
Vol 12 ◽  
Author(s):  
Haiyun Zhang ◽  
Ruijuan Guan ◽  
Zili Zhang ◽  
Defu Li ◽  
Jingyi Xu ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Cigarette Smoke ◽  
Mrna Stability ◽  
Molecular Mechanisms ◽  
Antisense Transcript ◽  
Alveolar Epithelium ◽  
Chronic Obstructive ◽  
Protein Coding ◽  
Obstructive Pulmonary Disease ◽  
Coding Potential

Evidence of the involvement of long noncoding RNAs (lncRNAs) in the pathogenesis of chronic obstructive pulmonary disease (COPD) is growing but still largely unknown. This study aims to explore the expression, functions and molecular mechanisms of Fantom3_F830212L20, a lncRNA that transcribes in an antisense orientation to Nqo1.We name this lncRNA as Nqo1 antisense transcript 1 (Nqo1-AS1). The distribution, expression level and protein coding potential of Nqo1-AS1 were determined. The effects of Nqo1-AS1 on cigarette smoke (CS)-induced oxidative stress were also evaluated. The results showed that Nqo1-AS1 were mainly located in the cytoplasm of mouse alveolar epithelium and had a very low protein coding potential. Nqo1-AS1 (or its human homologue) was increased with the increase of CS exposure. Nqo1-AS1 overexpression enhanced the mRNA and protein levels of Nqo1 and Serpina1 mRNA expression, and attenuated CS-induced oxidative stress, whereas knockdown of Nqo1-AS1 significantly decreased Nqo1 and Serpina1 mRNA expressions, and aggravated CS-induced oxidative stress. Nqo1-AS1 increased Nqo1 mRNA stability and upregulated Nqo1 expression through antisense pairing with Nqo1 3′UTR. In conclusion, these results suggest that Nqo1-AS1 attenuates CS-induced oxidative stress by increasing Nqo1 mRNA stability and upregulating Nqo1 expression, which might serve as a novel approach for the treatment of COPD.

scholarly journals Recent advances in pre-clinical mouse models of COPD

2013 ◽  
Vol 126 (4) ◽  
pp. 253-265 ◽  
Author(s):  
Ross Vlahos ◽  
Steven Bozinovski
Keyword(s):  
Chronic Inflammation ◽  
Cigarette Smoke ◽  
Mouse Models ◽  
Airflow Limitation ◽  
Cigarette Smoke Exposure ◽  
Chronic Obstructive ◽  
Small Airways ◽  
Obstructive Pulmonary Disease ◽  
New Therapies ◽  
Progression Of Disease

COPD (chronic obstructive pulmonary disease) is a major incurable global health burden and will become the third largest cause of death in the world by 2020. It is currently believed that an exaggerated inflammatory response to inhaled irritants, in particular cigarette smoke, causes progressive airflow limitation. This inflammation, where macrophages, neutrophils and T-cells are prominent, leads to oxidative stress, emphysema, small airways fibrosis and mucus hypersecretion. The mechanisms and mediators that drive the induction and progression of chronic inflammation, emphysema and altered lung function are poorly understood. Current treatments have limited efficacy in inhibiting chronic inflammation, do not reverse the pathology of disease and fail to modify the factors that initiate and drive the long-term progression of disease. Therefore there is a clear need for new therapies that can prevent the induction and progression of COPD. Animal modelling systems that accurately reflect disease pathophysiology continue to be essential to the development of new therapies. The present review highlights some of the mouse models used to define the cellular, molecular and pathological consequences of cigarette smoke exposure and whether they can be used to predict the efficacy of new therapeutics for COPD.

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

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.

scholarly journals FSTL1 aggravates cigarette smoke-induced airway inflammation and airway remodeling by regulating autophagy

2021 ◽  
Vol 21 (1) ◽  
Author(s):  
Ying Liu ◽  
Jiawei Xu ◽  
Tian Liu ◽  
Jinxiang Wu ◽  
Jiping Zhao ◽  
...  
Keyword(s):  
Lung Function ◽  
Airway Inflammation ◽  
Cigarette Smoke ◽  
Airway Remodeling ◽  
Critical Factor ◽  
Lavage Fluid ◽  
Chronic Obstructive ◽  
Obstructive Pulmonary Disease ◽  
Copd Patients ◽  
Impaired Lung Function

Abstract Background Cigarette smoke (CS) is a major risk factor for Chronic Obstructive Pulmonary Disease (COPD). Follistatin-like protein 1 (FSTL1), a critical factor during embryogenesis particularly in respiratory lung development, is a novel mediator related to inflammation and tissue remodeling. We tried to investigate the role of FSTL1 in CS-induced autophagy dysregulation, airway inflammation and remodeling. Methods Serum and lung specimens were obtained from COPD patients and controls. Adult female wild-type (WT) mice, FSTL1± mice and FSTL1flox/+ mice were exposed to room air or chronic CS. Additionally, 3-methyladenine (3-MA), an inhibitor of autophagy, was applied in CS-exposed WT mice. The lung tissues and serum from patients and murine models were tested for FSTL1 and autophagy-associated protein expression by ELISA, western blotting and immunohistochemical. Autophagosome were observed using electron microscope technology. LTB4, IL-8 and TNF-α in bronchoalveolar lavage fluid of mice were examined using ELISA. Airway remodeling and lung function were also assessed. Results Both FSTL1 and autophagy biomarkers increased in COPD patients and CS-exposed WT mice. Autophagy activation was upregulated in CS-exposed mice accompanied by airway remodeling and airway inflammation. FSTL1± mice showed a lower level of CS-induced autophagy compared with the control mice. FSTL1± mice can also resist CS-induced inflammatory response, airway remodeling and impaired lung function. CS-exposed WT mice with 3-MA pretreatment have a similar manifestation with CS-exposed FSTL1± mice. Conclusions FSTL1 promotes CS-induced COPD by modulating autophagy, therefore targeting FSTL1 and autophagy may shed light on treating cigarette smoke-induced COPD.

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