• 대한예방의학회:학술대회논문집
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• 대한예방의학회 1995년도 제47차 추계 학술대회 연제집
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• pp.247-248
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• 1995

• Tuberculosis and Respiratory Diseases
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• 제71권3호
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• pp.172-179
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• 2011

Background: Statins can regulate the production of pro-inflammatory cytokines and inhibit MMP production or activation in a variety of types of cells. This study evaluated whether statins would inhibit MMP release from human lung fibroblasts, which play a major role in remodeling processes. Methods: This study, using an in-vitro model (three-dimensional collagen gel contraction system), evaluated the effect of cytokines (tumor necrosis factor-${\alpha}$, TNF-a and interleukin-$1{\beta}$, IL-1b) on the MMP release and MMP activation from human lung fibroblasts. Collagen degradation induced by cytokines and neutrophil elastase (NE) was evaluated by quantifying hydroxyproline. Results: In three-dimensional collagen gel cultures (3D cultures) where cytokines (TNF-a and IL-1b) can induce the production of MMPs by fibroblasts, it was found that simvastatin inhibited MMP release. In 3D cultures, cytokines together with NE induced collagen degradation and can lead to activation of the MMP, which was inhibited by simvastatin. Conclusion: Simvastatin may play a role in regulating human lung fibroblast functions in repair and remodeling processes by inhibiting MMP release and the conversion from the latent to the active form of MMP.

• 한국환경성돌연변이발암원학회지
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• 제21권1호
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• pp.14-22
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• 2001

The detection of many synthetic chemicals used in industry that may pose a genetic hazard in our environment is of great concern at present. In this respect, administrative authorities has great concern to regulate and to evaluate the chemical hazard to environment and human health. The clastogenicity of 28 synthetic chemicals was evaluated in Chinese hamster lung fibroblast cells in vitro. Glycidylacrylate which is one of the most cytotoxic chemical among 28 chemicals tested revealed clastogenicity in the range of 0.31-1.25 $\mu\textrm{g}$/$m\ell$ both in the presence and absence of metabolic activation system. Neopentyl glycol (340-1360 $\mu\textrm{g}$/$m\ell$) also revealed weak positive result both in the presence and absence of metabolic activation system. Cyanoguanidine (/$420.5-841 $\mu\textrm{g}$m\ell$) and N-butylchloride ($231.5-926 $\mu\textrm{g}$/m\ell$) revealed weak positive result only in the absence of S-9 metabolic activation system. Nevertheless total aberration percentages of N-butylchloride in the presence of metabolic activation system, and 3,4＇-dichlorobenztrifluoride in the absence of S-9 metabolic activation revealed above 5% aberration, there is no statistical significance. From the results of chromosomal aberration assay with 28 synthetic chemicals in Chinese hamster lung cells, glycidylacrylate (CAS No. 106-90-0), neopentyl glycol (CAS No. 126-30-7), N-butyl chloride (CAS No. 109-69-3) and cyanoguanidine (CAS No. 461-58-5) revealed positive clastogenic results in this study.

• 한국환경성돌연변이발암원학회지
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• 제22권4호
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• pp.215-222
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• 2002

The detection of many synthetic chemicals used in industry that may pose a genetic hazard in our environment is of great concern at present. Since these substances are not limited to the original products, and enter the environment, they have become widespread environmental pollutants, thus leading to a variety of chemicals that possibly threaten the public health. In this respect, to regulate and to evaluate the chemical hazard will be important to environment and human health. The clastogenicity of 17 synthetic chemicals was evaluated in Chinese hamster lung fibroblast cells in vitro. Two most cytotoxic chemicals, dodecyl methacrylate (CAS No. 142-90-5) and 2-ethylhexyl methacrylate (CAS No. 688-84-6), among 17 chemicals tested revealed no clastogenicity in the range of 0.0165-0.066 $\mu\textrm{g}$/$m\ell$ and 0.006-0.024 $\mu\textrm{g}$/$m\ell$ both in the presence and absence of metabolic activation system, respectively. All 17 chemicals revealed no significant induction of chromosomal aberration both in the presence and absence of metabolic activation system in this assay. From the results of chromosomal aberration assay with 17 synthetic chemicals in Chinese hamster lung cells in vitro, we did not observed positive clastogenic results in this study.

• The Korean Journal of Physiology and Pharmacology
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• 제21권3호
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• pp.327-334
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• 2017

Epidemiologic interest in particulate matter (PM) is growing particularly because of its impact of respiratory health. It has been elucidated that PM evoked inflammatory signal in pulmonary epithelia. However, it has not been established $Ca^{2+}$ signaling mechanisms involved in acute PM-derived signaling in pulmonary fibroblasts. In the present study, we explored dust particles PM modulated intracellular $Ca^{2+}$ signaling and sought to provide a therapeutic strategy by antagonizing PM-induced intracellular $Ca^{2+}$ signaling in human lung fibroblasts MRC5 cells. We demonstrated that PM10, less than $10{\mu}m$, induced intracellular $Ca^{2+}$ signaling, which was mediated by extracellular $Ca^{2+}$. The PM10-mediated intracellular $Ca^{2+}$ signaling was attenuated by antioxidants, phospholipase blockers, polyADPR polymerase 1 inhibitor, and transient receptor potential melastatin 2 (TRPM2) inhibitors. In addition, PM-mediated increases in reactive oxygen species were attenuated by TRPM2 blockers, clotrimazole (CLZ) and N-(p-amylcinnamoyl) anthranilic acid (ACA). Our results showed that PM10 enhanced reactive oxygen species signal by measuring DCF fluorescence and the DCF signal attenuated by both TRPM2 blockers CLZ and ACA. Here, we suggest functional inhibition of TRPM2 channels as a potential therapeutic strategy for modulation of dust particle-mediated signaling and oxidative stress accompanying lung diseases.

• 대한한의학회지
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• 제20권2호
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• pp.88-97
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• 1999

To characterize the effects of Gilgyung-Tang(GGT) on cellular proliferation and viability of normal lung fibroblast cells, we examined the cell cycle progression and cell cycle-related gene expression in T3891 using a flow cytometry and a quantitative RT-PCR analysis. 1. The significant surpression effect of cellular proliferations of GGT was observed in proportion to a certain concentration and time. 2. GGT was identified to induce apoptotic death of damaged cells by treatment with a DNA-damage agent and etoposide, while it stimulated the recovery of cellular viability of normal cells. 3 The significant reductions of mRNA expression of PCAN, c-Fos treated by GGT were observed. 4. The significant inductions of mRNA expression of p53, CDKN1. Gadd45 treated by GGT were observed. 5. The apoptosis caused by the reduction of Bcl-2 genes was significant and the Bax genes were increased. but the amount of Fas genes were not changed. These results strongly suggest that GGT triggers arrest of the cell cycle at G1 phase, and thus causes an inhibition of cellular proliferation of human normal lung cells through the transcriptional up-regulation of cell cycle inhibitory genes and down-regulation of induction of cell cycle stimulating genes respectably.

• 한국환경독성학회:학술대회논문집
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• 한국환경독성학회 2003년도 춘계학술대회
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• pp.107-107
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• 2003

The heavy metal cadmium is a xenobiotic toxicant of environmental and occupational concern and it has been classified as a human carcinogen. Inhalation of cadmium has been implicated in the development of emphysema and pulmonary fibrosis, but, the detailed mechanism by which cadmium induces adverse biological effects is not yet known. Therefore, we undertook the investigation of genes that are induced after cadmium exposure to illustrate the mechanism of cadmium toxicity For this purpose, we employed the polymerase chain reaction-based suppression subtractive hybridization technique. We identified 29 different cadmium-inducible genes in human peripheral mononuclear cells, such as macrophage migration inhibitory factor, lysophosphatidic acid acyltransferase-${\alpha}$, enolase-1${\alpha}$, VEGF, Bax, neuron-derived orphan receptor-1, and Nur77, which are known to be associated with inflammation, cell survival, and apoptosis. Induction of these genes by cadmium treatment was further confirmed by semi-quantitative reverse-transcription polymerase chain reaction. Further, we found that these genes were also induced after cadmium exposure in normal human lung fibroblast cell line, WI-38, suggesting potential use of this induction profile to monitor cadmium toxicity in the lung. Next, Nur77, one of cadmium-inducible genes, was further studied since the products of Nur77 are known to be involved in the apoptotic process of lung cells. Following cadmium treatment, Nur77 gene expression was increased at protein-level in A549 cells. Consistently, the reporter containing Nur77 binding sequence was activated by 2.5-fold after exposure to cadmium in reporter gene analysis by transient transfection experiments. When the plasmid encoding dominant negative Nur77 that represses the transcriptional function of wild-type Nur77 was transfected into A549 cells, the expression of Bax was significantly reduced, suggesting that induction of Nur77 was an important process in cadmium-induced apoptosis in the cells. Cadmium induced the expression of Nur77 in vivo, confirming the relevance of the data obtained in viro. Together our results suggest that Nur77 gene expression in exposure to cadmium leads apoptosis of lung cells which may cause pathological changes in lung.

• 생명과학회지
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• 제24권8호
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• pp.837-842
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• 2014

이 연구의 목적은 사람 폐 섬유아세포인 IMR 90 에서 Brunfelsia grandiflora 에탄올 추출물(BGEE)이 SIRT1 및 p53 활성화를 통해 autophagy의 유도에 대한 효과를 조사한 것이다. BGEE는 $5{\mu}g/ml$ 이상의 농도에서 IMR 90 세포에서 세포독성을 나타내었다. 본 연구에서 처음으로 BGEE가 autophagy를 유도 하는 것이 발견되었다. 또한, BGEE는 $2.5{\mu}g/ml$ 이하에서 Beclin-1 및 $5{\mu}g/ml$ 이상에서 Atg7 의 활성화가 autophagy의 유도에 관여함을 확인하였다. 더욱이 BGEE는 autophagy와 관련된 단백질 발현을 조절하였는데 p53 및 p-p53 단백질 발현이 세포독성이 없는 농도의 BGEE존재하에서 감소되었다. 하였다. 반면에, SIRT1의 발현수준은 세포독성이 없는 농도의 BGEE로 처리된 IMR 90 세포에서 증가되었다. 더욱이 BGEE로 처리된 사람 페 섬유아세포에서 노화 마커의 지표인 SA-${\beta}$-gal staning이 감소되는 것이 관찰되었다. 이상의 발견들은 BGEE는 사람 폐 섬유아세포에서 p53 및 SIRT1의 조절을 통하여 autophagy 및 항노화 유발을 촉진 시키는 것을 시사하고 있다.

• Biotechnology and Bioprocess Engineering:BBE
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• 제10권6호
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• pp.556-563
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• 2005

Homogentisic acid was found to scavenge intracellular reactive oxygen species (ROS), and 1,1-diphenyl-2-picrylhydrazyl (DPPH) radicals and thus prevented lipid peroxidation in human fibroblast (Wl 38) cells. The radical scavenging activity of homogentisic acid was found to protect Wl 38 cells against hydrogen peroxide $(H_2O_2)$ induced oxidative stress, via the activation of extracellular signal regulated kinase (ERK) protein. Homogentisic acid increased the activity of catalase. Hence, from the present study, it is suggested that homogentisic acid protects Wl 38 cells against $H_2O_2$ damage by enhancing the intracellular antioxidative activity.

• Journal of Radiation Protection and Research
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• 제34권2호
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• pp.49-54
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• 2009

Mitochondrial DNA (mtDNA) deletion is a well-known marker for oxidative stress and aging and also contributes to their unfavorable effects in cultured cells and animal tissues. This study was conducted to investigate the effect of ionizing radiation (IR) on mtDNA deletion and the involvement of reactive oxygen species (ROS) in this process in human lung fibroblast (IMR-90) cells. Young IMR-90 cells at population doubling (PD) 39 were irradiated with $^{137}Cs$ $\gamma$-rays and the intracellular ROS level was determined by 2',7'-dichlorofluorescein diacetate (DCFH-DA) and mtDNA common deletion (4977bp) was detected by nested PCR. Old cells at PD 55 and $H_2O_2$-treated young cells were compared as the positive control. IR increased the intracellular ROS level and mtDNA 4977 bp deletion in IMR-90 cells dose-dependently. The increases of ROS level and mtDNA deletion were also observed in old cells and $H_2O_2$-treated young cells. To confirm the increased ROS level is essential for mtDNA deletion in irradiated cells, the effects of N-acetylcysteine (NAC) on IRinduced ROS and mtDNA deletion were examined. 5 mM NAC significantly attenuated the IR-induced ROS increase and mtDNA deletion. These results suggest that IR induces the mtDNA deletion and this process is mediated by ROS in IMR-90 cells.