• Tuberculosis and Respiratory Diseases
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• v.48 no.6
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• pp.898-908
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• 2000

Background : Eotaxin a CC chemokine specific for eosinophils, is implicated in the pathogenesis of asthma by recruiting eosinophils into the airways. Theophylline has been used for the treatment of asthma and recently was proposed to have an anti-inflammatory action. The aim of this study is to examine whether theophylline may inhibit the eosinophilic airway inflammation by reducing the expression of eotaxin. Methods : The expression of eotaxin mRNA was assessed by Northern analysis in A549 cells 4 h after stimulation with TNF-$\alpha$ or IL-1$\beta$. And then, theophylline was added to A549 cells stimulated with 0.1 ng/mL IL-1$\beta$. Results : Eotaxin mRNA expression rates induced by 0.1, 1, 10 ng/mL TNF-$\alpha$ as compared with $\beta$-actin, were 7%, 22%. 28%, respectively. Eotaxin mRNA expression rates induced by 0.01, 0.1, 1, 10 ng/mL IL-1$\beta$, as compared with $\beta$-actin, were 10%, 42%, 63%, 72%, respectively. Eotaxin mRNA expression rates after the addition of 0, 0.001, 0.01, 0.1 ${\mu}M$ dexamethasone induced by 10 ng/mL TNF-$\alpha$ as compared with $\beta$-actin, were 27%, 18%, 8%, respectively. Eotaxin mRNA expression rate after the addition of 0, 0.001, 0.01, 0.1 ${\mu}M$ dexamethasone induced by 0.1 ng/mL IL-1$\beta$ as compared with $\beta$-actin, were 43%, 47%, 12%, 8%, respectively. Eotaxin mRNA expression rates after the addition of 0, 0.001, 0.01, 0.1, 1, 10 mM theophylline induced by 0.1 ng/mL IL-1$\beta$, as compared with $\beta$-actin, were 48%, 40%, 33%, 22%, 16%, 14%, respectively. Conclusion : These results suggest that theophylline may reduce eosinophil infiltration of the airway at least in part by reducing the expression of eotaxin under the conditions of these experiments.

• Tuberculosis and Respiratory Diseases
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• v.64 no.5
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• pp.347-355
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• 2008

Background: IPF is characterized by chronic, fibrosing inflammatory lung disease of unknown etiology. Typical symptoms of IPF are exertional dyspnea with nonproductive cough. Why patients with typical IPF have dry cough rather than productive cough, is unknown. IP-10 plays an important regulatory role in leukocyte trafficking into the lung. The present study investigated the effect of IP-10 in the pathogenesis of dry cough rather than productive cough in IPF patients. Methods: IP-10 concentration was measured by ELISA from BALF of IPF patients. To evaluate the role of IP-10 in mucin expression, the expression of the MUC5AC mucin gene was measured in NCI-H292 cells, a human pulmonary mucoepidermoid carcinoma cell line, after stimulation by TNF-${\alpha}$ with or without IP-10 pretreatment. EGFR-MAPK expression was also examined as a possible mechanism. Results: IP-10 levels were significantly higher in the BALF of IPF patients compared to healthy controls. IP-10 pretreatment reduced TNF-${\alpha}$ induced MUC5AC mucin expression by inhibiting the EGFR-MAPK signal transduction pathway in NCI-H292 cells. Conclusion: These findings suggest that little mucus production in IPF patients might be attributable to IP-10 overproduction, which inhibits the EGFR-MAPK signal transduction pathway required for MUC5AC mucin gene expression.

• Tuberculosis and Respiratory Diseases
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• v.50 no.1
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• pp.76-83
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• 2001

Background : Coal workers' pneumoconiosis is a fibrotic lung disease resulting from chronic inhalation of coal dust. The precise mechanism of lung fibrosis in coal workers' pneumoconiosis is uncertain. However, a relationship between the stimulation of fibroblast proliferation and collagen production by mediators released from in flammatory and resident lung cells is thought to be a major factor. The transforming growth factor-$\beta$(TGF-$\beta$), a multifunctional cytokine and growth factor, plays a key role in the scarring and fibrotic processes due to its ability to induce extracellular matrix proteins and modulate the growth and immune function of many cell types. To determine the involvement of TGF-$\beta$ in the development of lung fibrosis in coal workers' pneumoconiosis, the TGF-${\beta}_1$ level in plasma was measured in patients with coal workers' pneumoconiosis. Methods : Plasma was collected from 40 patients with coal workers' pneumoconiosis (20 with simple coal workers' pneumoconiosis and 20 with complicated coal workers' pneumoconiosis) and from 10 normal controls. The ELISA method was used to measure the plasma TGF-${\beta}_1$ concentration. Results : Compared to the control group ($0.63{\pm}01.8$ ng/mL), there was no significant difference in the plasma TGF-${\beta}_1$ level in patients with simple coal workers' pneumoconiosis ($0.64{\pm}0.17$ ng/mL) (p>0.05). However, in patients with complicated coal workers' pneumoconiosis the plasma TGF-${\beta}_1$ level ($0.79{\pm}0.18$ ng/mL) was significantly higher than in patients with simple coal workers' pneumoconiosis and the control group (p<0.05). Conclusion : The data suggests that TGF-${\beta}_1$ has some influence in the development of lung fibrosis in coal workers' pneumoconiosis.

• Journal of Radiation Protection and Research
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• v.17 no.1
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• pp.21-30
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• 1992

The frequencies of KCCH cyclotron neutron (30 cGy/min) or $^{60}Co\;{\gamma}-rays$ (210 cGy/min)-induced asymmetrical interchanges (dicentrics and centric rings) and acentric fragments (deletion) at several doses were measured in the normal human peripheral blood lymphocytes Chromosome aberrations were scored at the first nitosis after stimulation with phytohemagglutinin. The neutron and y-ray data were analysed on linear, power-law, quadratic and linear-quadratic model . When the dicentrics and centric rings of ${\gamma}-rays$ datas were pooled and fitted to these model, good fits were obtained to power-law $[Y=(5.81{\pm}1.96){\times}10^6D^{1.93+0.06},\; P=0.931]$, quadratic $[Y=(3.91{\pm}0.09){\times}10^{-6}D^2,\;P=0.972]$ an linear-Quadrati model $[Y=(6.55{\pm}6.83){\times}10^{-5}D+(3.72{\pm}0.22){\times}10^{-6}D^2\; P=0.922]$, except for linear model (P=0.067) As in the case of neutron data, the best fit was obtained to the linear model $(Y=(6.12{\pm}0.17){\times}10^{-3}\;D-0.22,\;P=0.987]$ and good fits were obtained to power-law$[Y=(5.36{\pm}3.02) {\times}10^{-4}D^{1.42+0.11},\; P=0.601]$ and linear-quadratic model$[Y=(2.43{\pm}0.70){\times}10^{-3}D+(1.21{\pm}0.39){\times}10^{-7}D^2$, \;P=0.415], except for quadratic model (P<0.005). The relative biological effectiveness (RBE) of neutron compared with y-ray was estimated by best fitting model. In the asymmetrical interchanges range between 0.1 and 1.5 per cell, the RBE was found to be $2.714{\pm}0.408$.

• Tuberculosis and Respiratory Diseases
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• v.56 no.3
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• pp.289-296
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• 2004

Background : Mucus hypersecretion in the patients with airway diseases represents poor prognosis as well as discomfort. However, there is no known therapy for its effective control. One important component of mucus is mucin, a glycosylated protein, which endows mucus with viscosity. We studied whether a proteinase has a role in mucin secretion and if so, which. Methods : (1) Inhibition of mucin secretion Group-specific proteinase inhibitors were tested to evaluate whether a proteinase belonging to a group of proteinases plays a role in mucin secretion. Phenylmethylsulfonyl fluoride(PMSF, a serine proteinase inhibitor), E-64(a cysteine proteinase inhibitor), Pepstatin(an aspartic proteinase inhibitor) and 1, 10-Phenanthroline(a metalloproteinase inhibitor) were treated into the Calu-3 cell line for 24 hours. The enzyme linked immunoabsorbant assay(ELISA) for MUC5AC was performed to evaluate the amount of mucin secretion and to compare with a control. (2) Stimulation of mucin secretion Matrix metalloproteinase-9(MMP-9), MMP-12 and TACE(TNF-alpha converting enzyme), which are known to be related with airway diseases, were used to be treated into Calu-3 for 24 hours. ELISA for MUC5AC was performed to evaluate the amount of mucin secretion and to compare with the controls. Results : (1) PMSF($10^{-4}M$), E-64($10^{-4}M$), Pepstatin($10^{-6}M$) and 1, 10-Phenanthroline($10^{-4}M$) reduced the MUC5AC secretion by $1{\pm}4.9%$(mean${\pm}$standard deviation; P=1.0 compared with the control), $-6{\pm}3.9%$(P=0.34), $-13{\pm}9.7%$(P=0.34) and $41{\pm}8.2%$(P=0.03), respectively. (2) The amounts of MUC5AC secretion stimulated by MMP-9(250ng/ml), MMP-12(100ng/ml) and TACE(200ng/ml) were $103{\pm}6%$(P=0.39), $102{\pm}8%$(P=1.0) and $107{\pm}13%$(P=0.39), respectively, compared with the controls. Conclusion : Metalloproteinase(s) is (are) suggested to play a role in mucin secretion. It appears that metalloproteinases, other than MMP-9, MMP-12 or TACE, affect the mucin secretion in this in vitro model.

• Journal of Chest Surgery
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• v.23 no.3
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• pp.452-464
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• 1990

It is well known that extracellular Calcium plays a very important role in several steps of smooth muscle excitability and contractility, and there have been many concerns about factors influencing the distribution of extracellular Ca++ and the Ca++ flux through the cell membrane of the smooth muscle. Based on the assumption that Mg++ may also play an important role in the excitation and contraction processes of the smooth muscle by taking part in affecting Ca++ distribution and flux, many researches are being performed about the exact role of Mg++, especially in the vascular smooth muscle. But yet the effect of Mg++ in the smooth muscle activity is not clarified, and moreover the mechanism of Mg++ action is almost completely unknown. Present study attempted to clarify the effect of Mg++ on the excitability and contractility in the multiunit and unitary smooth muscle, and the mechanism concerned in it. The preparations used were the guinea-pig aortic strip as the experimental material of the multiunit smooth muscle and the rat uterine strip as the one of the unitary smooth muscle. The tissues were isolated from the sacrificed animal and were prepared for recording the isometric contraction. The effects of Mg++ and Ca++ were examined on the electrically driven or spontaneous contraction of the preparations. And the effects of these ions were also studied on the K+ or norepinephrine contracture. All experiments were performed in tris-buffered Tyrode solution which was aerated with 100% 02 and kept at 35oC. The results obtained were as follows: 1] Mg++ suppressed the phasic contraction induced by electrical field stimulation dose-dependently in the guinea-pig aortic strip, while the high concentration of Ca++ never recovered the decreased tension. These phenomena were not changed by the a - or b - adrenergic blocker. 2]Mg++ played the suppressing effect on the low concentration [20 and 40 mM] of K+-contracture in the aortic muscle, but the effect was not shown in the case of 100mM K+-contracture. 3] Mg++ also suppressed the contracture induced by norepinephrine in the aortic preparation. And the effect of Mg++ was most prominent in the contracture by the lowest [10 mM] concentration of norepinephrine. 4] In both the spontaneous and electrically driven contractions of the uterine strip, Mg++ decreased the amplitude of peak tension, and by the high concentration of Ca++ the amplitude of tension was recovered unlike the aortic muscle. 5] The frequency of the uterine spontaneous contraction increased as the [Ca++] / [Mg++] ratio increased up to 2, but the frequency decreased above this level. 6] Mg++ decreased the tension of the low[20 and 40mM] K+-contracture in the uterine smooth muscle, but the effect did not appear in the 100mM K+-contracture. From the above results, the following conclusion could be made. 1] Mg++ seems to suppress the contractility directly by acting on the smooth muscle itself, besides through the indirect action on the nerve terminal, in both the aortic and uterine smooth muscles. 2] The fact that the depressant effect of Mg++ on the K+-contracture is in inverse proportion to an increase of K+ concentration appears resulted from the extent of the opening state of the Ca++ channel. 3] Mg++ may play a depressant role on both the potential dependent and the receptor-operated Ca++ channels. 4] The relationship between the actions of Mg++ and Ca++ seems to be competitive in uterine muscle and non-competitive in aortic strip.

• Journal of Ginseng Research
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• v.30 no.2
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• pp.88-94
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• 2006

Ginseng as a raw material for production of probiotic ginseng product by lactic acid bacteria (LAB) was evaluated in this study. Either white ginseng (WG) or red ginseng (RG) (1% or 5%, w/v) were directly inoculated with a 24 hold seed culture of twenty seven substrains of four different LAB ($1.0{\times}10^6CFU/ml$); Lactobacillus spp., Streptococcus/Enterococcus spp., Leuconostoc/Lactococcus spp. and Bifidobacterium spp., and incubated at $37^{\circ}C$ for 24 or 48 h. Among 27 kinds of LAB, seven substrains of Lactobacillus (MG208, MG311, MG315, MG501, MG501C, MG505, MG590) and one Bifidobacterium (MG723) were selected based on their dose dependent stimulation of the growth of LAB in the presence of ginseng and changes in pH, acidity and viable cell counts during fermentation were examined. Lactobacillus MG208 specifically was found to show the best growth on 5% RG and reached nearly $14.0{\times}10^8CFU/ml$ after 48 h of fermentation and produced the titratable acidity as $0.84{\pm}0.02%$, whereas the pH was significantly lowered from $6.80{\pm}0.01\;to\;3.42{\pm}0.02$. These results indicated that ginseng can be an appropriate material to prepare the fermentation product by several strains of LAB. Therefore we should further check whether probiotic ginseng product may have synergistic health benefits of both probiotics and ginseng to serve for vegetarians and lactose-allergic consumers.

• Journal of the Society of Cosmetic Scientists of Korea
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• v.31 no.1 s.49
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• pp.97-102
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• 2005

One of the key molecules involved in skin moisture is hyaluronan (hyaluronic acid, HA) with its associated water of hydration. The predominant component of the ECM (extracellular matrix) of skin is HA. It Is the primordial and the simplest of the GAGs (glycosaminoglycans), a water-sorbed macromolecule In extracellular matrix, Included between the vital cells of epidermis. In the skin, HA was previously thought to derive extlusively from dermis. But, recent studies revealed that HA could be synthesized in epidermis. Flavonoids are polyphenolic compounds that is found mainly in foods of plant origin. Kaempferol was known to increase glutathione synthesis in human keratinocyte. And quercetin blocked PPAR-meidated keratinocyte differentiation as lipoxygenase inhibitors. In this study, we sought to evaluate the effect of flavonid, kaempferol and quercetin on production HA in keratinocyte. We examined the changes of three human hyaluronan synthase genes (HASI, HAS2, HAS3) expression by semi-quantitative RT-PCR when kaempferol or quercetin was added to cultured human keratinocytes. We found that these flavonoids slightly upregulated HAS2, HAS3 mRNA after 24 h. And we investigated the effect on HA production by ELISA. When we evaluated the level of HA in culture medium after 24 h incubation. We found enhanced accumulation of HA in the culture medium. Although the effects of above flavonoids are less than retinoic acid, the data indicate that kaempferol, quercetin can dose-dependently increase the level of HA in epidermis cell line. It suggested that flavonoid, kaempferol, and quercetin increased production of HA in skin and it helped to elevate skin moisture and improve facial wrinkle.

• Journal of the Society of Cosmetic Scientists of Korea
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• v.47 no.3
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• pp.205-212
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• 2021

The skin fibroblasts of different origins showed different expression levels of MMP-1 in response to TNF-α treatment or UV irradiation. We hypothesized that this is caused by polymorphism in the MMP-1 promoter region. To elucidate it, first of all, we analyzed and classified the genotype of the -1607 site of the MMP-1 promoter in 23 commercially available primary fibroblasts, and then we examined the expression of MMP-1 by TNF-α or UVB stimulation for each classified genotype. As a result of the analysis, fibroblasts with 6 1G/1G genotypes, 10 1G/2G genotypes, and 7 2G/2G genotypes were identified. Hs68 and Detroit 551 cell lines were confirmed to have 1G/2G genotypes. In the 1G/1G genotype, MMP-1 was expressed twice as high as that of the control group by TNF-α treatment, and was hardly expressed by UV light. In the case of the 1G/2G genotype, MMP-1 was expressed 2.45 fold higher by TNF-α treatment, and 1.4 fold by UV light than the control. In the case of the 2G/2G genotype, MMP-1 was expressed 1.35 fold by TNF-α treatment, and was highly expressed by 2.5 fold by ultraviolet rays compared to control. It can be estimated that MMP-1 expression is better induced in the 1G genotype by TNF-α and in the 2G genotype by UV light. In addition, it can be presumed that MMP-1 expression is increased by creating a site where the Ets transcription factor can bind by another G inserted at the -1607 position. These studies have not been conducted at all in fibroblasts in relation to skin aging, so it is an area that needs to be further studied in the future. In conclusion, since the skin is an organ that is affected by both intrinsic aging and photoaging at the same time, when analyzing the expression of MMP-1 as a target for improving skin aging, it is necessary to select cells with a genotype suitable for the experimental conditions of the study.

• Tuberculosis and Respiratory Diseases
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• v.82 no.1
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• pp.42-52
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• 2019

Background: Transforming growth factor ${\beta}$ (TGF-${\beta}$), retinoic acid (RA), p38 mitogen-activated protein kinase (MAPK), and MEK signaling play critical roles in cell differentiation, proliferation, and apoptosis. We investigated the effect of RA and the role of these signaling molecules on the phosphorylation of Smad2/3 (p-Smad2/3) induced by TGF-${\beta}1$. Methods: A549 epithelial cells and CCD-11Lu fibroblasts were incubated and stimulated with or without all-trans RA (ATRA) and TGF-${\beta}1$ and with MAPK or MEK inhibitors. The levels of p-Smad2/3 were analyzed by western blotting. For animal models, we studied three experimental mouse groups: control, bleomycin, and bleomycin+ATRA group. Changes in histopathology, lung injury score, and levels of TGF-${\beta}1$ and Smad3 were evaluated at 1 and 3 weeks. Results: When A549 cells were pre-stimulated with TGF-${\beta}1$ prior to RA treatment, RA completely inhibited the p-Smad2/3. However, when A549 cells were pre-treated with RA prior to TGF-${\beta}1$ stimulation, RA did not completely suppress the p-Smad2/3. When A549 cells were pre-treated with MAPK inhibitor, TGF-${\beta}1$ failed to phosphorylate Smad2/3. In fibroblasts, p38 MAPK inhibitor suppressed TGF-${\beta}1$-induced p-Smad2. In a bleomycin-induced lung injury mouse model, RA decreased the expression of TGF-${\beta}1$ and Smad3 at 1 and 3 weeks. Conclusion: RA had inhibitory effects on the phosphorylation of Smad induced by TGF-${\beta}1$ in vitro, and RA also decreased the expression of TGF-${\beta}1$ at 1 and 3 weeks in vivo. Furthermore, pre-treatment with a MAPK inhibitor showed a preventative effect on TGF-${\beta}1$/Smad phosphorylation in epithelial cells. As a result, a combination of RA and MAPK inhibitors may suppress the TGF-${\beta}1$-induced lung injury and fibrosis.