Decreased expression of antioxidant enzymes and increased expression of chemokines in COPD lung

Tomaki, Masafumi; Sugiura, Hiroaki; Koarai, Akira; Komaki, Yuichi; Akita, Takefumi; Matsumoto, Takuya; Nakanishi, Atsushi; Ogawa, Hiroyasu; Hattori, Toshio; Ichinose, Masakazu

doi:10.1016/j.pupt.2006.06.006

Cited by 65 publications

(53 citation statements)

References 26 publications

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“…Pulmonary diseases associated with a heightened risk of lung cancer, such as COPD and pulmonary fibrosis, show both increased and dysregulated inflammation [162,163]. Tobacco smoke exposure is associated with chronic airway inflammation and is the strongest risk factor for the development of lung cancer [17].…”

Section: Future Perspectivesmentioning

confidence: 99%

The Inflammatory Tumor Microenvironment, Epithelial Mesenchymal Transition and Lung Carcinogenesis

Heinrich

Walser

Krysan

et al. 2011

Cancer Microenvironment

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The inflammatory tumor microenvironment (TME) has many roles in tumor progression and metastasis, including creation of a hypoxic environment, increased angiogenesis and invasion, changes in expression of microRNAs (miRNAs) and an increase in a stem cell phenotype. Each of these has an impact on epithelial mesenchymal transition (EMT), particularly through the downregulation of E-cadherin. Here we review seminal work and recent findings linking the role of inflammation in the TME, EMT and lung cancer initiation, progression and metastasis.Finally, we discuss the potential of targeting aspects of inflammation and EMT in cancer prevention and treatment.

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Section: Future Perspectivesmentioning

confidence: 99%

The Inflammatory Tumor Microenvironment, Epithelial Mesenchymal Transition and Lung Carcinogenesis

Heinrich

Walser

Krysan

et al. 2011

Cancer Microenvironment

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“…Exposure to tobacco smoke increases inflammation, oxidative stress [1][2][3][4][5][6][7][8][9][10] and decreases antioxidant expression. [11][12][13][14][15] Direct and indirect studies have demonstrated that oxidative stress from reactive oxygen species (ROS) generated through mitochondria, xanthine oxidase, and the NADPH oxidase system [16][17][18][19][20][21] is one of the important factors in the pathogenesis of myocardial ischemia.…”

mentioning

confidence: 99%

Antioxidant N-acetyl cysteine reverses cigarette smoke-induced myocardial infarction by inhibiting inflammation and oxidative stress in a rat model

Khanna

Mehra

2012

Laboratory Investigation

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The contribution of chronic tobacco exposure in determining post-myocardial infarction (MI) left ventricular (LV) remodeling and possible therapeutic strategies has not been investigated systematically. In this small animal investigation, we demonstrate that chronic tobacco smoke exposure leading up to acute MI in rats is associated with greater histological extent of myocardial necrosis and consequent worse LV function. These findings are associated with increased transcriptomic expression of pro-inflammatory cytokines, tissue repair molecules and markers of oxidative stress in the myocardium. The results demonstrate that an N-acetyl cysteine (NAC) treatment significantly reduced tobacco-exposed induced infarct size and percent fractional shortening. A significantly increased LV end-systolic diameter was observed in tobacco-exposed sham compared to tobacco-naïve sham (4.92 ± 0.41 vs 3.45 ± 0.33; Po0.05), and tobacco-exposed MI compared to tobacco-naïve MI (8.24±0.3 vs 6.1±0.49; Po0.01) rats. Decreased intracardiac mRNA expression of the markers of inflammation, tissue repair and oxidative stress and circulating levels of pro-inflammatory cytokines accompanied these positive effects of NAC. The treatment of tobacco-exposed MI rats with NAC resulted in significantly increased levels of intracardiac mRNA expression of antioxidants, including superoxide dismutase, thioredoxin and nuclear factor-E2-related factor 2, as well as circulating levels of glutathione (7 ± 0.12 vs 10 ± 0.18; Pp0.001), where the levels were almost identical to the tobacco-naïve sham rats. These findings identify a novel post-infarction therapy for amelioration of the adverse effects of tobacco exposure on the infracted myocardium and advocate the use of dietary supplement antioxidants for habitual smokers to prevent and reverse cardiovascular adverse effects in the absence of successful achievement of cessation of smoking. Globally, tobacco smoke exposure remains a significant risk for the development of acute myocardial infarction (MI) irrespective of ethic or gender disparities. Exposure to tobacco smoke increases inflammation, oxidative stress 1-10 and decreases antioxidant expression. [11][12][13][14][15] Direct and indirect studies have demonstrated that oxidative stress from reactive oxygen species (ROS) generated through mitochondria, xanthine oxidase, and the NADPH oxidase system 16-21 is one of the important factors in the pathogenesis of myocardial ischemia. Decreased infarct size in superoxide dismutase (SOD)-producing transgenic mice suggests direct evidence for the role of involvement of ROS in MI. 22,23 In limited investigations, the use of antioxidants such as mercaptopropionyl glycine, edaravone and probucol have demonstrated varied effects on remodeling in animal models of MI, [24][25][26][27][28][29][30][31][32] with improvement in collagen content and histological changes. In this study, we sought to delineate the role of chronic tobacco smoke leading up to an acute MI by focusing on oxidative stress coupled with inflammat...

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“…The apical surface was rinsed with sterile phosphate-buffered saline and RNA was isolated from the cells. CCL2 in the sputum and lung tissue of patients with COPD (26)(27)(28). However, we show, for the first time, that this proinflammatory phenotype is maintained in early passage airway epithelial cells.…”

Section: Discussionmentioning

confidence: 60%

Increased Cytokine Response Of Rhinovirus-Infected Airway Epithelial Cells In Chronic Obstructive Pulmonary Disease

Schneider¹,

Comstock²,

Ganesan³

et al. 2010

C32. Rhinovirus and the Airways

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Rationale: Airway inflammation is a central feature of chronic obstructive pulmonary disease (COPD). COPD exacerbations are often triggered by rhinovirus (RV) infection. Objectives: We hypothesized that airway epithelial cells from patients with COPD maintain a proinflammatory phenotype compared with control subjects, leading to greater RV responses. Methods: Cells were isolated from tracheobronchial tissues of 12 patients with COPD and 10 transplant donors. Eight patients with COPD had severe emphysema, three had mild to moderate emphysema, and one had no emphysema. All had moderate to severe airflow obstruction, and six met criteria for chronic bronchitis or had at least one exacerbation the previous year. Cells were grown at airliquid interface and infected with RV serotype 39. Cytokine and IFN expression was measured by ELISA. Selected genes involved in inflammation, oxidative stress, and proteolysis were assessed by focused gene array and real-time polymerase chain reaction. Measurements and Main Results: Compared with control subjects, cells from patients with COPD demonstrated increased mRNA expression of genes involved in oxidative stress and the response to viral infection, including NOX1, DUOXA2, MMP12, ICAM1, DDX58/RIG-I, STAT1, and STAT2. COPD cells showed elevated baseline and RVstimulated protein levels of IL-6, IL-8/CXCL8, and growth-related oncogene-a/CXCL1. COPD cells demonstrated increased viral titer and copy number after RV infection, despite increased IL-29/IFN-l1, IL-28A/IFN-l2, and IFN-inducible protein-10/CXCL10 protein levels. Finally, RV-infected COPD cultures showed increased mRNA expression of IL28A/IFNl2, IL29/IFNl1, IFIH1/MDA5, DDX58/RIG-I, DUOX1, DUOX2, IRF7, STAT1, and STAT2. Conclusions: Airway epithelial cells from patients with COPD show higher baseline levels of cytokine expression and increased susceptibility to RV infection, despite an increased IFN response.

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Decreased expression of antioxidant enzymes and increased expression of chemokines in COPD lung

Cited by 65 publications

References 26 publications

The Inflammatory Tumor Microenvironment, Epithelial Mesenchymal Transition and Lung Carcinogenesis

The Inflammatory Tumor Microenvironment, Epithelial Mesenchymal Transition and Lung Carcinogenesis

Antioxidant N-acetyl cysteine reverses cigarette smoke-induced myocardial infarction by inhibiting inflammation and oxidative stress in a rat model

Increased Cytokine Response Of Rhinovirus-Infected Airway Epithelial Cells In Chronic Obstructive Pulmonary Disease

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