• Tuberculosis and Respiratory Diseases
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• v.59 no.5
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• pp.530-535
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• 2005

Background and Aims : Cigarette smoking induces an inflammatory response in the airways, which may play a key role in the pathogenesis of chronic obstructive pulmonary disease. Interleukin-6 (IL-6) is one of the cytokines that plays an important role in inducing bronchial inflammation. The aim of this study was to determine if the level of the pro-inflammatory cytokine, Interleukin-6, is increased when the bronchial epithelial cells are exposed to a cigarette smoke extract (CSE) and an extract from stop smoking-aiding cigarettes, and examined the safety of these commercially available stop smoking-aiding cigarettes. Method : Bronchial epithelial cells were exposed to CSE from cigarette and stop smoking-aiding cigarettes for 24 hours. ELISA was used to measure the IL-6 levels in the supernatant from each condition. The IL-6 mRNA levels were measured by Taqman Real time RT-PCR. N-acetyl-L-cysteine(NAC) was added to each condition to determine if NAC can inhibit the release of IL-6 from the bronchial epithelial cells when they are exposed to CSE from cigarette and stop smoking-aiding cigarettes. Result : When bronchial epithelial cells were exposed to a CSE from cigarettes and stop smoking-aiding cigarettes, each type of CSE stimulated IL-6 production from the bronchial epithelial cells. The IL-6 mRNA level in the Bronchial epithelial cells was also elevated and NAC was found to inhibit the release of IL-6 from bronchial epithelial cells when they were exposed to the CSE from cigarettes and stop smoking-aiding cigarettes. Conclusion : Commercially available stop smoking-aiding cigarette can induce bronchial inflammation and can be harmful to smokers. Therefore, the safety of these cigarettes for smoking cessation should be evaluated.

• Journal of the Korean Society of Tobacco Science
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• v.29 no.2
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• pp.85-89
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• 2007

This study was conducted to evaluate the prediction of sensory characteristics of smoke from the leaf chemical compounds and characterize leaf chemical components for the best tobacco taste's leaves in oriental tobacco. For analytical and sensory evaluations, seventy two grades were used. Sensory evaluation of tobacco smoke for six attributes were scored on fifteen-point scale by $10{\sim}14$ expert panels trained to estimate smoking quality quantitatively. The major leaf chemical compounds to predict the sensory characteristics of smoke were ether extract for tobacco-like, nicotine for impact and total nitrogen/nicotine ratio for irritation, and total sugar for off taste & odor. Within ${\pm}20%$ range of difference, the predictable probabilities of sensory characteristics of smoke from the leaf chemical compounds were 87.5 % for off taste & odor and $94.4{\sim}98.6\;%$ for tobacco-like, impact and irritation. As a result of K-means cluster analysis on the basis of tobacco taste, the desirable leaf chemical compound contents were $5.9{\sim}8.3\;%$ in ether extract, $1.35{\sim}2.27\;%$ in nicotine and $1.17{\sim}2.24$ in total nitrogen/nicotine ratio. This study suggest that the some regression equations may be useful to predict the sensory characteristics of tobacco smoke with a few selected leaf chemical compounds in oriental tobacco and to select the oriental tobacco leaves by means of enhancing the tobacco taste of cigarette.

• IMMUNE NETWORK
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• v.24 no.2
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• pp.3.1-3.23
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• 2024

Cigarette smoke extract (CSE)-treated mouse airway epithelial cells (MAECs)-derived exosomes accelerate the progression of chronic obstructive pulmonary disease (COPD) by upregulating triggering receptor expressed on myeloid cells 1 (TREM-1); however, the specific mechanism remains unclear. We aimed to explore the potential mechanisms of CSE-treated MAECs-derived exosomes on M1 macrophage polarization and pyroptosis in COPD. In vitro, exosomes were extracted from CSE-treated MAECs, followed by co-culture with macrophages. In vivo, mice exposed to cigarette smoke (CS) to induce COPD, followed by injection or/and intranasal instillation with oe-TREM-1 lentivirus. Lung function and pathological changes were evaluated. CD68⁺ cell number and the levels of iNOS, TNF-α, IL-1β (M1 macrophage marker), and pyroptosis-related proteins (NOD-like receptor family pyrin domain containing 3, apoptosis-associated speck-like protein containing a caspase-1 recruitment domain, caspase-1, cleaved-caspase-1, gasdermin D [GSDMD], and GSDMD-N) were examined. The expression of maternally expressed gene 3 (MEG3), spleen focus forming virus proviral integration oncogene (SPI1), methyltransferase 3 (METTL3), and TREM-1 was detected and the binding relationships among them were verified. MEG3 increased N6-methyladenosine methylation of TREM-1 by recruiting SPI1 to activate METTL3. Overexpression of TREM-1 or METTL3 negated the alleviative effects of MEG3 inhibition on M1 polarization and pyroptosis. In mice exposed to CS, EXO^-CSE further aggravated lung injury, M1 polarization, and pyroptosis, which were reversed by MEG3 inhibition. TREM-1 overexpression negated the palliative effects of MEG3 inhibition on COPD mouse lung injury. Collectively, CSE-treated MAECs-derived exosomal long non-coding RNA MEG3 may expedite M1 macrophage polarization and pyroptosis in COPD via the SPI1/METTL3/TREM-1 axis.

• The Korean Journal of Physiology and Pharmacology
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• v.26 no.2
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• pp.95-111
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• 2022

Chronic obstructive pulmonary disease (COPD) is an important healthcare problem worldwide. Often, glucocorticoid (GC) resistance develops during COPD treatment. As a classic hypoglycemic drug, metformin (MET) can be used as a treatment strategy for COPD due to its anti-inflammatory and antioxidant effects, but its specific mechanism of action is not known. We aimed to clarify the role of MET on COPD and cigarette smoke extract (CSE)-induced GC resistance. Through establishment of a COPD model in rats, we found that MET could improve lung function, reduce pathological injury, as well as reduce the level of inflammation and oxidative stress in COPD, and upregulate expression of nuclear factor E2-related factor 2 (Nrf2), heme oxygenase-1 (HO-1), multidrug resistance protein 1 (MRP1), and histone deacetylase 2 (HDAC2). By establishing a model of GC resistance in human bronchial epithelial cells stimulated by CSE, we found that MET reduced secretion of interleukin-8, and could upregulate expression of Nrf2, HO-1, MRP1, and HDAC2. MET could also increase the inhibition of MRP1 efflux by MK571 significantly, and increase expression of HDAC2 mRNA and protein. In conclusion, MET may upregulate MRP1 expression by activating the Nrf2/HO-1 signaling pathway, and then regulate expression of HDAC2 protein to reduce GC resistance.

• Korean Journal of Medicinal Crop Science
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• v.25 no.4
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• pp.201-208
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• 2017

Background: The present study was carried out to asses whether mulberry leaves (MLs) have the potential to inhibit the mutagenic effect of cigarette smoke condensates (CSCs). Methods and Results: ML powder was extracted with 70% ethanol, and a yield of 35.1% by weight was obtained. The 70% ethanol extract of ML was further extracted sequentially using diethyl ether, chloroform, butanol, dichloromethane and water. The crude 70% ethanol extract of MLs and its solvent fractions did not show any mutagenic effect when tested at concentrations up to 1 mg/plate against Salmonella typhimurium TA98. In contrast, the crude 70% ethanol extract showed an inhibitory activity against the mutagenicity of CSCs in the presence of S-9 mixture. Among the solvent fractions, the diethyl ether fraction showed the highest inhibitory activity, which increased in a dose-dependent manner, inhibiting mutagenesis by approximately 97.1% at a concentration of 1 mg/plate. Conclusions: In this study, we found that a crude 70% ethanol extract of MLs and the diethyl ether fraction themselves are potentially not mutagenic, but inhibit the mutagenic effect of CSCs.

• Journal of Ginseng Research
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• v.19 no.3
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• pp.225-230
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• 1995

The effect of long-term ginseng (Panax ginseng C.A. Meyer) administration on the clearance of carboxyhemoglobin (CO-Hb) and the property of blood gases was investigated in rats. Rats were received ginseng water extract (0.025% in drinking water) for 42 weeks starting at the age of 6 weeks. They were exposed to the diluted mainstream smoke generated from 15 filter cigarettes for 20 min in a round polycarbonate chamber (D37 cmXH13 cm). Under this condition, the mean CO-Hb content of control and the ginseng-treated rats immediately after the exposure was nearly the same as 13.8$\pm$2.9 f) and 13.9$\pm$1.6%, respectively. However, CO-Hb was more rapidly removed from blood in the ginseng treated rats than in untreatEd control with the laps of time, namely, its biological half life In the former was 36.9$\pm$1.5 min and in the latter was 56.9$\pm$13.2 min. Although long-term ginseng treatment did not affect the content of hemoglobin and blood pH of rats, it slightly increased blood oxygen content and its partial pressure value, and decreased levels of carbon dioxide and bicarbonate. These results suggest that long-term administration of rats with ginseng extract accelerate the elimination of CO from the blood. This effect seems to be related to the enhancement of oxygen consumption of the rat by a certain action of ginseng components as previously reported.

• Tuberculosis and Respiratory Diseases
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• v.58 no.1
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• pp.43-53
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• 2005

Emphysema is characterized by air space enlargement and alveolar destruction. The mechanism responsible for the development of emphysema was thought to be protease/antiprotease imbalance and oxidative stress. A very recent study shows that alveolar cell apoptosis causes lung destruction and emphysematous changes. Thus, this study was performed to support the evidence for the role of apoptosis in the development of emphysema by characterizing cigarette smoke extract (CSE)-induced apoptosis in A549 (type II pneumocyte) lung epithelial cells. CSE induced apoptosis at low concentration (10% or less) and both apoptosis and necrosis at high concentration (20%). Apoptosis was demonstrated by DNA fragmentation using FACScan for subG1 fraction. Discrimination between apoptosis and necrosis was done by morphologic analysis using fluorescent microscopy with Hoecst 33342/propium iodide double staing and electron microscopy. Cytochrome c release was confirmed by using immunofluorescence with monoclonal anti-cytochrome c antibody. However, CSE-induced cell death did not show the activation of caspase 3 and was not blocked by caspase inhibitors. This suggests that CSE-induced apoptosis might be caspase-independent apoptosis. CSE-induced cell death was near completely blocked by N-acetylcystein and bcl-2 overexpression protected CSE-induced cell death. This results suggests that CSE might induce apoptosis through intracellular oxidative stress. CSE also activated p53 and functional knock-out of p53 using stable overexpression of HPV-E6 protein inhibited CSE-induced cell death. The characterization of CSE-induced cell death in lung epithelial cells could support the role of lung cell apoptosis in the pathogenesis of emphysema.

• Tuberculosis and Respiratory Diseases
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• v.58 no.6
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• pp.590-599
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• 2005

Object : Cigarette smoking is a major cause of mucus hypersecretion, which is a pathophysiological feature of many inflammatory airway diseases. Mucins, which are an important part of the airway mucus, are synthesized from the Muc gene in airway epithelial cells. However, the signaling pathways for cigarette smoke-induced mucin synthesis are unknown. The aim of this study was to determine the signal pathway for smoking induced Muc5ac gene expression. Methods : A549 cells were cultured and transiently transfected with the Muc5ac promoter fragment. These cells were stimulated with 5% cigarette smoke extract (CSE) alone or with CSE after a pretreatment with various signal transduction pathway inhibitors (AG1478, PD98059 and SB203580). The Muc5ac promoter activity was examined using the luciferase reporter system, and the level of phosphorylated EGFR, ERK1/2, p38 MAPK and JNK were all examined using Western blot analysis. Muc5ac mRNA expression was also examined using reverse transcriptase polymerase chain reactions (RT-PCR). Results : 1. The peak level of luciferase activity of the Muc5ac promoter was observed at 5% concentration and after 3 hours of incubation with the CSE. The level of EGFR phosphorylation and the luciferase activity of the transfected cells caused by the CSE were significantly suppressed by AG1478 or PD98059 (P<0.01). 2. CSE phosphorylated ERK1/2 or p38 MAPK but not JNK. The Muc5ac mRNA expression level was increased by the CSE but that was suppressed by PD98059 or AG1478. 3. The CSE-induced phosphorylation of ERK1/2 was blocked by PD98059 and that of p38 MAPK was blocked by either PD98059 or SB203580. Either PD98059 or SB203580 suppressed the luciferase activity of the transfected cells (P<0.0001). Conclusion : The Muc5ac mRNA expression level was increased by the CSE. The increased CSE-induced transcriptional activity was mediated via EGF receptor activation, which led to ERK1/2 and p38 MAPK phosphorylation.

• Korean Journal of Food Science and Technology
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• v.24 no.3
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• pp.193-198
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• 1992

The inhibitory effects of radish juice on the mutagenicities of cigarette smoke condensate (CSC), methanol extract of charred part of fried or broiled saury pike (MECS) and 2-aminofluorene (2-AF) were examined by the use of Ames assay toward Salmonella typhimurium TA 98 strain. Radish juice exhibited inhibition percentage of about 100, 100 and 87 on the mutagenicities of CSC, two kinds of MECS and 2-AF, respectively. Except for juices of cabbage and leek, radish juice has inhibited more effectively the mutagenicity of CSC than other fruit or vegetable juices studied. Inhibitory effect of radish juice might be originated from the components with molecular weight above 50,000 and decreased sharply in 5 min by heat treatment at $100^{\circ}C$, but hardly changed at low and moderate storage temperatures such as $4^{\circ}C,\;10^{\circ}C,\;25^{\circ}C\;and\;35^{\circ}C$ for about 2 weeks. Precipitate obtained from ammonium sulfate saturation from 30 to 80% had inhibitory effect on the mutagenicity of CSC. Extracts from 3 bands of non-denaturing gel of $30{\sim}80%$ amnonium sulfate precipitate have exhibited the inhibitory effects on the mutagenicity of CSC.

• Tuberculosis and Respiratory Diseases
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• v.70 no.6
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• pp.462-473
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• 2011

Background: Smoking is a risk factor for idiopathic pulmonary fibrosis (IPF), but the mechanism of the association remains obscure. There is evidence demonstrating that plasminogen activator inhibitor-1 (PAI-1) is involved in the progression of pulmonary fibrosis. This study was to determine whether the administration of small interfering RNA (siRNA) targeting PAI-1 or PAI-1 inhibitor to the cigarette smoking extract (CSE)-exposed rat alveolar type II epithelial cells (ATII cells) limits the epithelial-mesenchymal transition (EMT). Methods: ATII cells were isolated from lung of SD-rat using percoll gradient method and cultured with 5% CSE. The EMT was determined from the ATII cells by measuring the real-time RT PCR and western blotting after the PAI-1 siRNA transfection to the cells and after administration of tiplaxtinin, an inhibitor of PAI-1. The effect of PAI-1 inhibitor was also evaluated in the bleomycin-induced rats. Results: PAI-1 was overexpressed in the smoking exposed ATII cells and was directly associated with EMT. The EMT from the ATII cells was suppressed by PAI-1 siRNA transfection or administration of tiplaxtinin. Signaling pathways for EMT by smoking extract were through the phosphorylation of SMAD2 and ERK1/2, and finally Snail expression. Tiplaxtinin also suppressed the pulmonary fibrosis and PAI-1 expression in the bleomycin-induced rats. Conclusion: Our data shows that CSE induces rat ATII cells to undergo EMT by PAI-1 via SMAD2-ERK1/2-Snail activation. This suppression of EMT by PAI-1 siRNA transfection or PAI-1 inhibitor in primary type II alveolar epithelial cells might be involved in the attenuation of bleomycin-induced pulmonary fibrosis in rats.