• Biomolecules & Therapeutics
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• 제29권1호
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• pp.58-63
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• 2021

Asthma is a chronic obstructive lung disease characterized by recurrent episodes of bronchoconstriction and wheezing. Conventional asthma treatment involves the suppression of airway inflammation or improving airway flow. Rosmarinus officialis, also known as rosemary, is a Mediterranean plant that is used for the treatment of inflammatory diseases. Carnosol, a diterpenoid found in rosemary extracts, has been known to exhibit anti-inflammatory, anti-tumor, and anti-oxidant effects. The effect of carnosol on allergic responses has not been tested yet. The effect of carnosol on a murine allergic asthma model were investigated. Carnosol inhibited the degranulation of RBL-2H3 mast cells. Carnosol treatment inhibited the increase in the number of eosinophils in the bronchoalveolar lavage fluids (BALF) of mice treated with ovalbumin. Carnosol treatment also inhibited inflammatory responses and mucin production in histologic studies. Carnosol treatment inhibited the increases of IL-4 and IL-13 cytokines expression in both BALF and the lungs. These results suggest that carnosol may have a potential for allergic asthma therapy.

• Tuberculosis and Respiratory Diseases
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• 제48권4호
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• pp.464-470
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• 2000

연구배경 : 기관지 천식은 기도의 과민성과 만성 염증반응을 보이는 질환이다. 저자들은 sIL-6R 및 IL-6 혈중치의 변화를 측정하여 이들의 변화가 증상 악화시 기관지 천식의 병인과 판련이 있는지에 대하여 연구하고자 하였다. 방 법 : 1998년 3월 부터 1999년 3월까지 기관지 천식으로 치료중인 환자중에서 증상 악화로 응급실을 경유하여 전북대학교 병원 내과에 입원한 급성 천식 환자 78예와 무증상 천식 환자 15예 그리고 정상인 10예를 대상으로 하였다. 환자의 병력과 임상 소견, 피부반응검사, 그리고 IgE 및 호산구수를 측정하고 endogen ELISA Kit ($Quantikine^{(R)}sIL$-6R, IL-6)를 이용하여 sIL-6R, IL-6을 측정하였다. 결 과 : 혈청내 IL-6와 sIL-6R농도는 급성 천식 환자에서 대조군에 비해 유의 있는 증가를 보였으며, 무증상 천식 환자와 비교할 때 IL-6의 의미있는 증가를 보였다. 또한 급성 천식 환자에서 혈청내 IL-6와 sIL-6R간에 유의한 상관 관계가 있었다. 하지만 급성 천식환자에서의 IgE와 호산구수는 IL-6 및 sIL-6R와 유의한 상관관계가 없었다. 결 론 : 혈청내 IL-6는 급성 천식의 병태 생리에 관여 할 수 있으며, IL-6와 sIL-6R의 혈청치는 기도 염증의 중증도를 예측하는 표식자로 유용할 것으로 생각된다.

• Journal of Ginseng Research
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• 제45권4호
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• pp.482-489
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• 2021

Background: Asthma is an incurable hyper-responsive disease of the pulmonary system that is caused by various allergens, including indoor and outdoor stimulators. According to the Global Asthma Network, 339 million people suffered from asthma in 2018, with particularly severe forms in children. Numerous treatments for asthma are available; however, they are frequently associated with adverse effects such as growth retardation, neurological disorders (e.g., catatonia, poor concentration, and insomnia), and physiological disorders (e.g., immunosuppression, hypertension, hyperglycemia, and osteoporosis). Methods: Korean Red Ginseng has long been used to treat numerous diseases in many countries, and we investigated the anti-asthmatic effects and mechanisms of action of Korean Red Ginseng. Eighty-four BALB/c mice were assigned to 6 treatment groups: control, ovalbumin-induced asthma group, dexamethasone treatment group, and 3 groups treated with Korean Red Ginseng water extract (KRGWE) at 5, 25, or 50 mg/kg/day for 5 days. Anti-asthmatic effects of KRGWE were assessed based on biological changes, such as white blood cell counts and differential counts in the bronchoalveolar lavage fluid, serum IgE levels, and histopathological changes in the lungs, and by examining anti-asthmatic mechanisms, such as the cytokines associated with Th1, Th2, and Treg cells and inflammation pathways. Results: KRGWE affected ovalbumin-induced changes, such as increased white blood cell counts, increased IgE levels, and morphological changes (mucous hypersecretion, epithelial cell hyperplasia, inflammatory cell infiltration) by downregulating cytokines such as IL-12, IL-4, and IL-6 via GATA-3 inactivation and suppression of inflammation via NF-κB/COX-2 and PGE₂ pathways. Conclusion: KRGWE is a promising drug for asthma treatment.

• Tuberculosis and Respiratory Diseases
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• 제51권6호
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• pp.530-539
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• 2001

연구배경 : 기관지 천식은 기도의 재구성과 관련된 기도의 염증성 질환이다. Vascular endothelial growth factor(VEGF) 는 혈관생성과 염증반응에 관여하는 강력하고 다양한 기능의 사이토카인이며 Matrix metalloproteinase-9(MMP-9)은 기관지 천식에서 기도의 재구성을 일으키는 주요 단백분해 효소이다. 그러나, 아직 급성 기관지 천식에서 VEGF의 역할 및 VEGF와 MMP-9의 관련성등에 관한 보고는 거의 없다. 저자들은 급성 기관지 천식에서 VEGF가 기관지 염증반응에 관여하는지를 조사하였고 또한 객담내 VEGF 발현 정도와 MMP-9의 관련성도 같이 알아보고자 하였다. 방 법 : 저자들은 안정상태 및 급성천식상태 환자에서 객담내 VEGF와 MMP-9의 양을 효소 면역측정과 zymography 분석으로 측정하였고 또한 기관지 천식의 자발 발작시에도 측정하였다. 결 과 : 기관지 천식 환자군에서 안정상태의 천식환자군이나 건강 대조군보다 객담내 VEGF 양이 유의있게 높음을 알 수 있었고 또한 천식 발작시에는 안정시보다 더 유의있게 높았으며 천식치료후 점차 감소하였다. 급성 천식 환자들에서 객담내 VEGF농도는 호중구및 호산구들 수와 의의있게 관련이 있었고 또한 객담내 VEGF와 MMP-9의 농도사이에 유의있는 상관관계가 있음을 알 수 있었다. 결 론 : 급성 기관지 천식 환자에서 VEGF의 과도발현은 기도 염증반응과 관련이 있으며 또한 MMP-9과도 밀접한 연관성이 관련성이 있는 것으로 사료된다.

• Tuberculosis and Respiratory Diseases
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• 제57권5호
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• pp.425-433
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• 2004

연구배경 : 경구면역관용 유도는 4주 이내의 급성천식모델에서 알레르기 염증반응을 효과적으로 억제하는 것으로 알려져 있다. 하지만 경구면역관용 유도가 4주 이상 지속되는 만성천식모델에서도 알레르기 염증반응을 효과적으로 억제할 수 있는 지에 대해서는 아직 불확실하다. 본 연구에서는 8주 동안 지속되는 만성천식모델을 이용하여 경구면역관용 유도가 알레르기 염증반응 및 기도재형성에 어떤 영향을 미치는 지를 관찰하였다. 방 법 : 5주된 암컷 BALB/c 마우스에 ovalbumin(OVA)을 복강 내로 투여하여 감작시킨 후, 6주 동안 주 2회 OVA를 반복 흡입시킴으로써 만성천식모델을 만들었다. 경구면역관용은 감작시키기 전에 OVA를 경구 투여함으로써 유도하였으며, 저용량 군(OVA 1 $mg/day{\times}6$일)과 고용량 군(OVA 25 $mg/day{\times}1$일)으로 나누었다. 기도과민성은 농도별 메타콜린 흡입에 따른 enhanced pause (penh) 값의 변화로 평가하였으며, 기관지폐포세척액 내의 염증세포수를 측정하고 IL-13, IFN-${\gamma}$ 농도 및 혈청 내 OVA 특이 IgE, IgG1, IgG2a 농도를 ELISA로 측정하였다. 기도재형성 정도는 폐조직의 PAS 및 Masson's trichrome 염색으로 관찰하였다. 결 과 : 경구면역관용군은 천식군에 비해 penh 값, 기관지폐포세척액 내의 염증세포 수, IL-13 및 IFN-${\gamma}$ 농도, 혈청 내의 OVA 특이 IgE, IgG1 및 IgG2a 농도, 폐조직 술잔세포의 과다형성, 기저막하부의 섬유화 정도가 유의하게 감소되었다 (P<0.05). 결 론 : 알레르기 기관지천식모델에서 경구면역관용 유도는 8주까지 장기적으로 기도과민성, 염증반응 및 기도재 형성을 억제하였으며, 그 기전에는 항원 특이 면역글로불린과 Th1 및 Th2 시토카인들에 대한 억제작용이 중요한 역할을 하는 것으로 추측되었다.

• Clinical and Experimental Pediatrics
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• 제56권1호
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• pp.8-12
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• 2013

Asthma is associated with increased levels of eosinophils in tissues, body fluids, and bone marrow. Elevated levels of eosinophil-derived neurotoxin (EDN) and eosinophil cationic protein (ECP) have been noted in asthma patients. Higher levels of EDN and ECP are also associated with exacerbated asthmatic conditions. Thus, EDN, along with ECP, may aid the diagnosis and monitoring of asthma. Several groups have suggested that EDN is more useful than ECP in evaluating disease severity. This may partially be because of the recoverability of EDN (not sticky, 100% recovery rate), as ECP is a sticky and more highly charged protein. In terms of clinical utility, EDN level is a more accurate biomarker than ECP when analyzing the underlying pathophysiology of asthma. As a monitoring tool, EDN has shown good results in children with asthma as well as other allergic diseases. In children too young to fully participate in lung function tests, EDN levels may be useful as an alter native measurement of eosinophilic inflammation. EDN can also be used in adult patients and in multiple specimen types (e.g., serum, sputum, bronchoalveolar lavage fluid, and nasal lavage fluid). These results are repeatable and reproducible. In conclusion, EDN may be a novel biomarker for the diagnosis, treatment, and monitoring of asthma/allergic disease.

• Tuberculosis and Respiratory Diseases
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• 제57권6호
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• pp.543-552
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• 2004

연구배경 : 급성천식 동물모델에 투여할 경우 특징적인 기도과민성이나 호산구성 염증 등이 호전되는 것으로 알려져 있으나, 만성천식 모델에서 기도의 만성염증 및 기도재구성을 억제할 수 있다는 연구는 많지 않다. CpG-ODN이 기도의 만성염증 및 기도재구성을 예방할 수 있는 지 알기위하여, 만성천식 마우스모델에서 CpG-ODN의 기도의 만성염증 및 기도재구성에 대한 영향을 연구하고자 하였다. 방 법 : BALB/C 마우스를 ovalbumin으로 감작시킨뒤 7주간 만성적인 자극을 주어 만성 천식모델을 만들고, CpG-ODN은 감작시에 복강내에 주사하였다. 7주후기 도저항(기도과민성)의 측정, 혈청 IgE의 측정, 기관지 폐포세척액에서 염증세포분획을 검사하였고, 폐조직검사로 염증세포의 침윤 및 기저막하부의 섬유화의 정도를 관찰하였고, OVA군과 CpG-ODN군과 비교하였다. 결 과 : 1) 기관지폐포세척액내 호산구는 CpG-ODN군은 OVA군에 비해 통계적으로 유의하게 감소하였다($0.9{\pm}0.8$ ; $9.7{\pm}5.8{\times}10^4/ml$, P<0.01). 2) 기도과민성은 CpG-ODN군은 OVA군에 비해서 기도과민성(Penh)이 $50mg/m{\ell}$를 제외한 농도에서 모두 유의하게 감소한 소견을 보였다(P<0.01). 3) 혈청 총 IgE는 CpG-ODN군이 OVA군에 비해 감소한 소견을 보였고($0.21{\pm}0.11$ ; $1.16{\pm}0.39{\mu}g/ml$, P<0.01), 혈청 OVA specific IgE도 CpG-ODN군이 OVA군에 비해 감소한 소견을 보였다($1.1{\pm}0.5$ ; $1.7{\pm}0.6$ OD units, P<0.01). 4) 배상세포의 증식정도는 CpG-ODN군은 OVA군에 감소된(P<0.01) 소견을 보였다. 5) 기저막하부의 섬유화의 정도는 CpG-ODN군이 OVA군에 비해서 유의하게 감소된(P<0.01) 소견을 보였다. 결 론 : CpG-ODN은 기도의 급성염증 및 기도과민성을 억제할 뿐만 아니라 만성천식 마우스모델에서 기도의 만성염증 및 기도재구성을 억제시킴을 알 수 있었다.

• 대한본초학회지
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• 제30권3호
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• pp.1-12
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• 2015

Objectives : In this study, we investigated the effects of Agastachis Herba water (AH-W) extract on compound 48/80-induced mast cell degranulation and histamine release in human mast cells and also anti-asthmatic effect of AH-W extract on ovalbumin (OVA)-induced asthma in mice. Methods : Human mast cells, HMC-1 were treated with AH-W extract in the presence or absence of compound 48/80 (C48/80). Mast cell degranulation was observed by microscope, and the histamine release was measured in culture medium by ELISA. For preparation of asthmatic in vivo model, mice were sensitized (0, 7, and 14 days) with OVA and airway challenged (21, 23, 25, 27, and 29 days). AH-W extract at doses of 100 and 300 mg/kg/body weight was orally administered during OVA challenge once per a day. The levels of immunoglobulin (Ig) E, and Th1/Th2 cytokines, IFN-$\gamma$ and IL-4 were measured in the sera of mice by ELISA. The histopathological change of lung tissues was observed by hematoxylin and eosin (H&E) and Periodic Acid Schiff (PAS) staining. Results : The treatment of AH-W extract significantly decreased the mast cell degranulation and histamine release in C48/80-stimulated HMC-1 cells. In addition, The administration of AH-W extract at does of 100 and 300 mg/kg significantly decreased the serum levels of OVA-specific IgE compared with those of OVA control group. In H&E and PAS staining, AH-W extract inhibited OVA-induced airway inflammation, and inflammatory cells infiltration, and also histopathological damages on lung tissues such as bronchiole epithelial desquamation, goblet cells hyperplasia, and mucin releasing. Conclusions : These results indicate that AH-W extract may improve asthmatic symptoms through mast cell stabilization and inhibiting the lung inflammation in bronchial asthma.

• 대한본초학회지
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• 제28권1호
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• pp.65-71
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• 2013

Objectives : Asthma is a chronic, complex respiratory disease, caused by airway obstruction, airway eosinophilic inflammation(AEI), and airway hyperresponsiveness(AHR). This study was conducted to determine whether oral administration of crude water extracts of Pinellia ternate Breitenbach(PTB) has an antiasthmatic potential in the treatment of asthma in mice. Methods : Asthmatic AEI and AHR were induced by systemic sensitization to ovalbumin(OVA) by intratracheal instillation with 0.1 mg/mL suspension of diesel exhaust particles(DEP) once a week for 10 weeks in BALB/c mice. Crude PTB water extracts(50 mg/kg and 200 mg/kg) were orally administered 5 times a week for 10 weeks. Cyclosporin(10 mg/kg) was administrered the same manner as a positive control. Results : Long-term treatment with crude PTB water extracts suppressed the infiltration of inflammatory cells, including eosinophils, into airways from blood. It also reduced asthmatic AEI and AHR by attenuating the increase in the levels of cytokines such as interleukin(IL)-4, IL-5 and IL-13 in bronchoalveolar lavage fluid(BALF), as well as the levels of histamine and OVA-specific IgE in blood. However, the effect of crude PTB water extracts(200 mg/kg) was not likely to be stronger than that of cyclosporin(10 mg/kg). Conclusion : These results suggest that crude PTB water extracts have inhibitory effects on AEI and AHR in a mouse model of asthma and may act as a potential Th2 cytokine antagonist, and have a therapeutic effect on allergic asthma.

• Clinical and Experimental Pediatrics
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• 제54권9호
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• pp.373-379
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• 2011

Purpose: 4-1BB (CD 137) is a costimulatory molecule expressed on activated T-cells. Repression by 4-1BB is thought to attenuate Th2-mediated allergic reactions. The aim of this study was to investigate the effect of 4-1BB on allergic airway inflammation in a murine asthma model. Methods: BALB/c mice were sensitized to and challenged with ovalbumin (OVA). Hu.4-1BB-Fc was administered 1 day before the first OVA sensitization or 1 day after the second OVA sensitization. Following antigen challenge, airway responsiveness to methacholine was assessed and bronchoalveolar lavage (BAL) fluid was analyzed. Total immunoglobulin (Ig) E, OVA-specific IgE, $IgG_1$, and $IgG_{2a}$ levels in sera were measured by enzyme-linked immunosorbent assay. Lung pathology was also evaluated. Results: In mice treated with Hu.4-1BB-Fc before the first OVA sensitization, there was a marked decrease in airway hyperresponsiveness, total cell count, and eosinophil count in the BAL fluid. In addition, Hu.4-1BB-Fc treatment decreased serum OVA-specific $IgG_1$ levels and increased serum $IgG_{2a}$ level significantly compared with the corresponding levels in mice sensitized to and challenged with OVA. Hu.4-1BB-Fc-treated mice also showed suppressed peribronchial and perivascular inflammatory cell infiltration. In contrast, treatment with Hu.4-1BB-Fc 1 day after sensitization had no effect on airway hyperresponsiveness and showed less suppression of inflammation in lung tissue. Conclusion: Administration of Hu.4-1BB-Fc can attenuate airway inflammation and hyperreactivity in a mouse model of allergic airway inflammation. In addition, administration before sensitization may be more effective. These findings suggest that 4-1BB may be a useful therapeutic molecule against asthma.