• Tuberculosis and Respiratory Diseases
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• 제43권1호
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• pp.46-53
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• 1996

연구배경: 폐포대식세포가 내독소에 노출되면 이 후 자극에 의해 종양괴사인자, 활성산소 등 독성이 강한 분비물 방출이 더욱 촉진되어 성인성호흡곤란증후군과 같은 각종 폐질환이 초래되는 중요한 기전으로 이해되고 있다. 그러나 문헌에 보고된 내독소에 의한 이런 priming효과는 다형핵백혈구, 단핵세포나 동물의 폐포대식세포를 대상으로 한 결과로서, 인체 폐포내에서의 폐포대식세포, 폐포상피세포 및 내독소의 상호작용을 밝히는 면에서는 한계가 있었다. 방법: 폐포상피세포에서 기원한 폐암세포주인 A549 24-well Linbro plate에 배양하여 세포단층을 형성한 후 기관지폐포세척술로 얻은 사람의 폐포대식세포($10^6/ml$)를 A549세포에 부착시켜 생체내와 유사한 환경을 만들어 실험을 시행하였다. 방법은 A549세포 부착 전후에 내독소(500 ng/ml)로 전처치한 다음 PMA, fMLP로 자극하여 방출된 과산화수소를 nM/well/2hrs 단위로 측정하여 대조군과 비교하였고 아울러 A549세포만종 없이 각 well에 직접 폐포대식세포단층을 형성한 후 동일하게 처치하였으며 결과는 다음과 같았다. 결과: 1) 24-well의 표면에 폐포대식세포단층을 형성한 후 내독소로 처치(n=7)한 경우, 대조군은 무자극군, PMA 자극군, fMLP자극군에서 각각 $9.48{\pm}2.44$, $10.38{\pm}2.34$, $10.28{\pm}2.33$ nM/well/2hrs의 과산화수소 분비능을 보였고 내독소 전처치군은 각각 $9.56{\pm}2.15$, $9.82{\pm}1.80$, $11.31{\pm}2.48$ nM/well/2hrs을 보여 내독소에 의한 priming효과는 없었다. 2) 폐포대식세포를 미리 내독소로 처치한 후 A549세포단층에 부착(n=7)시킨 경우에는 대조군의 과산화수소 분비능은 무자극군 $4.82{\pm}1.59$, PMA자극군 $8.31{\pm}1.67$, fMLP자극군 $7.06{\pm}1.82$ nM/well/2hrs이고 내독소 전처치군은 각각 $4.44{\pm}1.41$, $7.05{\pm}1.64$, $6.32{\pm}1.69$ nM/well/2hrs로서 내독소에 의한 priming 효과는 없었다. 3) 폐포대식세포를 A549세포단층에 부착시킨 후 내 독소로 처치(n=11)하면 대조군은 무자극군, PMA자극군, fMLP자극군에서 각각 $4.33{\pm}1.04$, $7.94{\pm}1.42$, $6.00{\pm}1.22$ nM/well/2hrs의 과산화수소를 분비하였고 내독소 전처치군은 각각 $5.43{\pm}1.19$, $7.56{\pm}1.31$, $6.38{\pm}1.19$ nM/well/2hrs를 보여 A549세포 부착후에도 내독소의 priming 효과는 관찰되지 않았으나 PMA나 fMLP로 자극하지 않은 무자극군에서 내독소 전처치군이 대조군에 비해 과산화수소 분비능의 유의한 증가를 보였다(p<0.05). 결론: 이상의 결과는 사람 폐포대식세포에서 내독소에 의한 priming효과는 없으나 폐포상피세포와의 상호작용에 의해 내독소가 폐포대식세포를 직접 자극함을 시사하는 소견이며 향후 추시가 필요할 것으로 사료된다.

• 대한치과교정학회지
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• 제17권2호
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• pp.223-248
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• 1987

The early tissue reactions in the periodontal tissues of the tension zones following the application of force (30gm) to the maxillary first molar teeth of the albino rats were studied by the light microscopy and electron microscopy The increase of periodontal fibroblasts was evident, particularly in 1 day survival period. Osteoblast differentiation and new bone formation on the alveolar bone surface were occurred from 1 day survival period. Mononuclear phagocytes occurred consistently and in relatively high number adjacent to and at some distance from blood vessel Extensive breakdown of collagen fibers was observed. The increase of the phagocytosis of collagen by the active fibroblasts was evident Also, collagen fibrils were sparse or lost near the macrophage.

• 대한한방종양학회지
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• 제5권1호
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• pp.77-101
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• 1999

l. Sojeokbaekchoolsan compound treatment decreased pulmonary fibrosis induced by Bleomycin. 2. At 1 and 2 days after bleomycin treatment, Sojeokbaekchoolsan compound treatment decreased the number of neutrophils in bronchoalveolar lavage than those of bleomycin alone treatment. 3. Sojeokbaekcoolsan compound treatment increased the Fc receptor mediated rosette activity of alveolar macrophage decreased by bleomycin treatment. 4, At 10 days after bleomycin treatment, Sojeokbaekchoolsan compound treatment decreased the lipid peroxidation of lung tissue than those of bleomycin alone treatment. 5. Anti-tumor activity of Sojeokbaekchoolsan and bleomycin compound group was higher than those of bleomycin alone treated group to ascitic tumor caused by Sarcoma-180 tumor cells.

• Tuberculosis and Respiratory Diseases
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• 제45권1호
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• pp.36-44
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• 1998

연구배경: IFN-$\gamma$는 단핵식세포를 활성화시키며 여러 종류의 세포내 세균에 대한 숙주의 방어기전에 중요한 역할을 하는 것으로 알려져있다. 그러나 사람에 있어서 IFN-$\gamma$의 항 결핵 효과와 작용기전에 대해서는 거의 알려진 바가 없다. 본 연구에서는 결핵의 발병기전에서 IFN-$\gamma$의 역할을 알아보기 위해 폐포대식세포의 결핵균 탐식과 TNF-$\alpha$ 생산에 IFN-$\gamma$가 미치는 영향을 알아보았다. 방 법: 활동성 폐질환이 없는 8명의 사람에게서 얻은 기관지 폐포세척액에서 폐포대식세포를 표면흡착법으로 분리하여 결핵균과 같이 배양하면서 ($1{\times}10^6$ cells/ml, $3{\times}10^7$ bacteria/ml) 배양액에 IFN-$\gamma$(300U/ml), LPS(0.5ug/ml), 자가혈청(10%)을 첨가하여 2시간 배양 후 항산성 염색(modified Kynion method)을 하여 결핵균을 탐식한 폐포대식세포를 관찰하였다. 그리고 폐포대식세포배양액에 IFN-$\gamma$(300U/ml), MTB($1{\times}106bacteria/ml$) and LPS(0.5ug/ml)를 각각 첨가하여 24시간 배양 후 상층액에서 TNF-$\alpha$의 농도를 ELISA method로 측정하였다. 그리고 IFN-$\gamma$(300U/ml), LPS(0.5ug/ml)로 24시간 자극한 폐포대식세포의 결핵균 탐식율도 관찰하였다. 결 과: IFN-$\gamma$는 폐포대식세포의 결핵균 탐식율을 증가시키지 않았으며(percentage of PAM-phagocytosed MTB: control: $22.1{\pm}4.9$, IFN-$\gamma$: $20.3{\pm}5.3$), 폐포대식세포를 24시간 자극하였을 때 폐포대식세포의 TNF-$\alpha$의 생산을 증가시키지 않았다 (control: $21{\pm}38pg/ml$, IFN-$\gamma$: $87{\pm}106pg/ml$). 그리고 IFN-$\gamma$로 24 시간 전처치한 폐포대식세포의 결핵균 탐식율 또한 증가하지 않았다(control: $24.5{\pm}9.5$, IFN-$\gamma$: $23.4{\pm}10.1$). 결 론: IFN-$\gamma$는 폐포대식세포의 결핵균 탐식과 TNF-$\alpha$ 생산에 영향을 미치지 않는다.

• Tuberculosis and Respiratory Diseases
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• 제70권2호
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• pp.113-124
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• 2011

Background: Macrophages are one of the most important inflammatory cells in innate immunity. PU.1 is a macrophage-specific transcription factor. Ubiquitins are the ultimate regulator of eukaryotic transcription. The ubiquitination process for PU.1 is unknown. This study investigated the lipopolysaccharide (LPS)-induced activation of PU.1 and its relation to ubiquitins in the macrophages. Methods: Raw264.7 cells, the primary cultured alveolar, pulmonary, and bone marrow derived macrophages were used. The Raw264.7 cells were treated with MG-132, $NH_4Cl$, lactacytin and LPS. Nitric oxide and prostaglandin D2 and E2 were measured. Immunoprecipitation and Western blots were used to check ubiquitination of PU.1. Results: The PU.1 ubiquitination increased after LPS ($1{\mu}g$/mL) treatment for 4 hours on Raw264.7 cells. The ubiquitination of PU.1 by LPS was increased by MG-132 or $NH_4Cl$ pretreatment. Two hours of LPS treatment on macrophages, PU.1 activation was not induced nor increased with the inhibition of proteasomes and/or lysosomes. The ubiquitination of PU.1 was increased in LPS-treated Raw264.7 cells at 12- and at 24 hours. LPS-treated cells increased nitric oxide production, which was diminished by MG-132 or $NH_4Cl$. LPS increased the production of $PGE_2$ in the alveolar and peritoneal macrophages of wild type mice; however, $PGE_2$ was blocked or diminished in Rac2 null mice. Pretreatment of lactacystin increased $PGE_2$, however it decreased the $PGD_2$ level in the macrophages derived from the bone marrow of B57/BL6 mice. Conclusion: LPS treatment in the macrophages ubiquitinates PU.1. Ubiquitination of PU.1 may be involved in synthesis of nitric oxide and prostaglandins.

• 한국약용작물학회지
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• 제25권5호
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• pp.269-281
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• 2017

Background: Small particles increase airway inflammation upon reaching the alveoli. Here, we investigated the protective or therapeutic effects of Salvia plebeia R. Br. (SP_R) extracts on airway inflammation. Methods and Results: To investigate the anti-inflammatory activity of SP_R extracts, we measured their inhibitory effect on the production of reactive oxygen species (ROS) expression of inflammatory mediators, and immune cell infiltration in MH-S alveolar macrophage cells and in the ambient particulate matter (APM)-exposed airway inflammation mice model. The SP_R extracts inhibited the production of ROS and expression of IL-4, IL-10, IL-15, and IL-17A mRNA in APM-stimulated MH-S cells. Oral administration of SP_R extracts suppressed APM-induced inflammatory symptoms, such as high alveolar wall thickness, excess collagen fibers, decreased mRNA expression of chemokines (Ccr9, Ccl5, Ccr3), inflammatory cytokines (IL-15, TNF-${\alpha}$), and IL-4 Th2 cytokine in the lung. The SP_R extracts also inhibited ROS production, granulocyte ($CD11b^+Gr-1^+$) infiltration, IL-17A, TNF-${\alpha}$, macrophage inflammatory protein (Mip-2), and chemokine (C-X-C motif) ligand 1 (Cxcl-1) production in the airway. The specific compounds in the SR-R extracts that mediate the anti-inflammatory effects were identified. Conclusions: In this study, SP_R extracts effectively inhibited airway inflammatory responses, such as ROS production and granulocyte infiltration into the airway, by regulating the expression of chemokines and inflammatory cytokines.

• 대한수의학회지
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• 제63권3호
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• pp.27.1-27.9
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• 2023

Lespedeza cuneata (LC) is a perennial plant used in herbal medicine to treat numerous diseases, including prostatic hyperplasia, diabetes, early atherosclerosis, and hematuria. Reference collections of bioactive compounds of LC are crucial for the determination of their pharmacological properties. However, little is known regarding its anti-oxidative and anti-inflammatory effects in alveolar macrophage (MH-S) cells. This study examined whether LC can inhibit reactive oxygen species and Coal fly ash (CFA) induced inflammation in MH-S cells. The anti-oxidative effects of LC were evaluated using 1,1-diphenyl-2-picrylhydrazyl (DPPH) and 2,2'-azino-bis(3-ethylbenzothiazoline-6-sulfonic acid) (ABTS) assays, anti-inflammatory effects were examined using nitric oxide (NO) assay, and cytotoxicity was analyzed using methyl thiazolyl tetrazolium assay. The expression of inflammatory cytokine genes was assessed through a reverse-transcription polymerase chain reaction. Our results revealed that LC exhibited high radical scavenging activity and a dose-dependent (7.8-1,000 ㎍/mL) inhibition of oxidation as compared to ascorbic acid and Trolox. It also inhibited CFA-induced NO production in MH-S cells. Moreover, it suppressed the CFA exposure-mediated expression of pro-inflammatory mediators and cytokines, including inducible nitric oxide synthase (iNOS), cyclooxygenase-2 (COX-2), interleukin (IL)-1β, IL-6, and tumor necrosis factor-α. These results suggest that LC is a potent antioxidant and anti-inflammatory agent that can be useful as a nutraceutical product.

• 동의생리병리학회지
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• 제25권1호
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• pp.55-64
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• 2011

The object of this study was to observe the effects of Scutellariae Radix (SR) aqueous extracts on lipopolysaccharide (LPS)-induced rat acute lung injury. Five different dosages of SR extracts were orally administered once a day for 28 days before LPS treatments, and then 5 hours after lipopolysaccharide treatment, all rats were sacrificed. 8 groups, each of 16 rats per group were used in the present study. Changes on the body weights, lung weights, pulmonary transcapillary albumin transit, arterial gas parameters (pH, $PaO_2$ and $PaCO_2$) bronchoalveolar lavage fluid (BALF) protein, lactate dehydrogenase (LDH) and proinflammatory cytokines tumor necrosis factor-${\alpha}$ (TNF-${\alpha}$), interleukin-1${\beta}$ (IL-1${\beta}$) contents, total cell numbers, neutrophil and alveolar macrophage ratios, lung malondialdehyde (MDA), myeloperoxidase (MPO), proinflammatory cytokine TNF-${\alpha}$ and IL-1${\beta}$ contents were observed with histopathology of the lung, changes on luminal surface of alveolus (LSA), thickness of alveolar septum, number of polymorphonuclear neutrophils (PMNs). The results were compared with a potent antioxidant ${\alpha}$-lipoic acid, 60 mg/kg, in which the effects on LPS-induced acute lung injury were already confirmed. The results obtained in this study suggest that over 125 mg/kg of SR extracts showed favorable effects on the LPS-induced acute lung injury, and 250 mg/kg of SR extracts resembling acute respiratory distress syndrome mediated by their antioxidant and anti-inflammatory effects and .as similar to ${\alpha}$-lipoic acid in the present study. Therefore, it is expected that SR will be showed favorable effects on the acute respiratory distress syndrome.

• Tuberculosis and Respiratory Diseases
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• 제45권4호
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• pp.888-895
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• 1998

Malaria is one of the most common infectious diseases in the world. Plasmodium falciparum, accounting for nearly all malaria mortality, kills an estimated 1 to 2 million persons yearly and has several features that make it deadlist of malarias. While cerebral malaria is the most common presentation of severe disease, acute lung injury associated with malaria is uncommon but serious and fatal complication. We report two cases of severe malaria with ARDS and multi-organ failure. All two patients traveled to foreign countries, Kenya, Papua New Guinea where choroquine-resistant malaria is distributed. The first case, which developed cerebral malaria, hypoglycemia, multi-organ failure, and ARDS, treated with quinine and mechanical ventilator, but expired due to oxygenation failure. Autopsy showed acute necrotizing infiltration, diffuse eosinophilic fibrinoid deposits along the alveolar space, and alveolar macrophage with malaria pigment The second case also developed multi-organ failure, followed by ARDS, and was treated with quinine, exchange transfusion, plasmapheresis, and mechanical ventilator. He recovered with residual restrictive lung change after treatment.

• Experimental and Molecular Medicine
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• 제50권11호
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• pp.9.1-9.10
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• 2018

Although the positive effects of recombinant fibroblast growth factor-2 (rFGF-2) in chronic obstructive pulmonary disease (COPD) have been implicated in previous studies, knowledge of its role in COPD remains limited. The mechanism of FGF2 in a COPD mouse model and the therapeutic potential of rFGF-2 were investigated in COPD. The mechanism and protective effects of rFGF-2 were evaluated in cigarette smoke-exposed or elastase-induced COPD animal models. Inflammation was assessed in alveolar cells and lung tissues from mice. FGF-2 was decreased in the lungs of cigarette smoke-exposed mice. Intranasal use of rFGF-2 significantly reduced macrophage-dominant inflammation and alveolar destruction in the lungs. In the elastase-induced emphysema model, rFGF-2 improved regeneration of the lungs. In humans, plasma FGF-2 was decreased significantly in COPD compared with normal subjects (10 subjects, P = 0.037). The safety and efficacy of inhaled rFGF-2 use was examined in COPD patients, along with changes in respiratory symptoms and pulmonary function. A 2-week treatment with inhaled rFGF-2 in COPD (n = 6) resulted in significantly improved respiratory symptoms compared with baseline levels (P < 0.05); however, the results were not significant compared with the placebo. The pulmonary function test results of COPD improved numerically compared with those in the placebo, but the difference was not statistically significant. No serious adverse events occurred during treatment with inhaled rFGF-2. The loss of FGF-2 production is an important mechanism in the development of COPD. Inhaling rFGF-2 may be a new therapeutic option for patients with COPD because rFGF-2 decreases inflammation in lungs exposed to cigarette smoke.