• Journal of Microbiology
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• 제43권1호
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• pp.11-16
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• 2005

Matrix metalloproteinase (MMP)-9 plays an important role in the pathogenesis of bronchial asthma. Neovastat, having significant antitumor and antimetastatic properties, is classified as a naturally occurring multifunctional antiangiogenic agent. We evaluated the therapeutic effect of Neovastat on airway inflammation in a mouse model of asthma. BALB/c mice were immunized subcutaneously with ovalbumin (OVA) on days 0, 7, 14, and 21 and challenged with inhaled OVA on days 26, 29, and 31. Neovastat was administrated by gavage (5 mg/kg body weight) three times with 12 h intervals, beginning 30 min before OVA inhalation. On day 32, mice were challenged with inhaled methacholine, and enhanced pause (Penh) was measured as an index of airway hyperresponsiveness. The severity of airway inflammation was determined by differential cell count of bronchoalveolar lavage (BAL) fluid. The MMP-9 concentration in BAL fluid samples was measured by ELISA, and MMP-9 activity was measured by zymography. The untreated asthma group showed an increased inflammatory cell count in BAL fluid and Penh value compared with the normal control group. Mice treated with Neovastat had significantly reduced Penh values and inflammatory cell counts in BAL fluid compared with untreated asthmatic mice. Furthermore, mice treated with Neovastat showed significantly reduced MMP-9 concentrations and activity in BAL fluid. These results demonstrate that Neovastat might have new therapeutic potential for airway asthmatic inflammation.

• Tuberculosis and Respiratory Diseases
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• 제53권2호
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• pp.101-112
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• 2002

연구배경 : 알레르기성 천식에서 기관지 재모형의 기전이 세포외 기질 침착에 의한다는 것은 잘 알려져 있다. MMP족중 특히 MMP-9은 천식의 기관지 재모형을 유발하는 주요 단백분해 효소이다. 또한, MMP-9은 기저막을 통한 호산구와 중성구의 이동을 유발한다고 알려져 있다. 최근에는 MMP가 천식의 쥐 모형에서 기도 과민성의 유발과 oval bumin 유발성 기도 염증 세포의 침윤에 있어서 중요한 역할을 한다고 보고되어졌다. 그러나, TDI 유발성 천식에 있어서 MMP의 역할에 대한 유효한 자료는 거의 없는 실정이다. 연구방법 : 특정 항원이 없는 암컷 BALB/c 쥐를 약간 변형된 Sugawara 등의 방법에 따라 ethyl acetate에 3% TDI를 녹인 용액을 5일 연속 매일 한번씩 비강내 주입하여 쥐를 감작시켰다. 기관지폐포 세척액의 채취하여 세포 분석과 MMPs의 측정하였고 폐조직에서 면역화학적 검사를 시행하였다. MMP 억제재를 TDI 부하(challenge) 30분전에 시작하여 24시간 간격으로 3회 복강내로 (10 또는 20mg/kg) 주입하고 기도 반응도를 측정하였다. 결 과 : TDI 감작 부하군에서 기관지폐포 세척액 염증 세포수와 MMP-9 및 폐조직의 면역화학적 검사상 MMP-9의 발현의 유의한 증가가 관찰되었다. MMP 억제재투여후 TDI 감작 부하군에서 기관지 폐포 세척액 염증 세포수와 MMP-9 및 폐조직의 면역화학적 검사상 MMP-9의 발현의 유의한 감소를 보였고 기도 과민성을 억제하였다. 결 론 : 본 연구의 결과는 MMP 억제재가 TDI 유발성 천식에 대한 훌륭한 치료제로서 향후 연구의 가치가 있음을 강력히 시사한다.

• 한국약용작물학회지
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• 제23권3호
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• pp.237-244
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• 2015

In this study, essential oils were extracted from the leaf of Chamaecyparis obtusa (CLEO), indigenous to Korea, CLEO constituents were analysed, and the effects of CLEO on airway hyperresponsiveness (AHR) and airway inflammation (AI) were investigated in Ovalbumin (OVA)-induced asthma mouse model. Terpenoid components among identified CLEO constituents made up more than 80%. The CLEO-treated group in comparison to the control group showed reduced AHR, the decrease of eosinophil number in the bronchoalveolar lavage fluid (BALF), reduced specific anti-OVA IgE level in the serum, and a significant reduction in Th2 cytokines levels in the BALF with concentration. We concluded that CLEO have an alleviating effect on asthma-like symptoms such as AHR and AI. Further studies about antiasthmatic effect are necessary on the focus of single component of CLEO.

• 동의생리병리학회지
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• 제18권3호
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• pp.841-845
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• 2004

This experiment was designed to investigate the effect of Gamcho(Glycyrrhiza uralensis Fisch, GLU) in asthma. We measured histamine, IL-1β, IL-4, 1L-5, IL-6, IL-10, IL-13, in plasma of ovalbumin induced asthmatic mouse. The results were obtained as follows: GLU decreased the proliferation of histamine, IL-1β, IL-4, IL-5, IL-6, IL-13 significantly. GLU increased the proliferation of IL-10 significantly. According to the above results, it is suggested that GLU extract might be useful applied for prevention and treatment of allergic asthma.

• 동의생리병리학회지
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• 제18권2호
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• pp.463-467
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• 2004

This experiment was designed to investigate the effect of Gamcho(Glycyrrhiza uralensis Fisch, GLU) on Antiallergy in asthma. We measured IL-4, IL-5, UL-13, IgE in bronchoalveolar lavage fluid of ovalbumin induced asthmatic mouse and observed murine lung tissue. The results were obtained as follows: 1. GLU decreased the proliferation of IL-4, IL-5, IL-13, IgE significantly. According to the above results, it is suggested that GLU extract might be useful applied for prevention and treatment of allergic asthma.

• Clinical and Experimental Pediatrics
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• 제56권11호
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• pp.482-489
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• 2013

Purpose: The aim of the present study was to investigate the differences in lower airway inflammatory immune responses, including cellular responses and responses in terms of inflammatory mediators in bronchoalveolar lavage fluid (BALF) and the airway, to rhinovirus (RV) infection on asthma exacerbation by comparing a control and a murine asthma model, with or without RV infection. Methods: BALB/c mice were intraperitoneally injected with a crude extract of Dermatophagoides farinae (Df ) or phosphate buffered saline (PBS) and were subsequently intranasally treated with a crude extract of Df or PBS. Airway responsiveness and cell infiltration, differential cell counts in BALF, and cytokine and chemokine concentrations in BALF were measured 24 hours after intranasal RV1B infection. Results: RV infection increased the enhanced pause (Penh) in both the Df sensitized and challenged mice (Df mice) and PBS-treated mice (PBS mice) (P<0.05). Airway eosinophil infiltration increased in Df mice after RV infection (P<0.05). The levels of interleukin (IL) 13, tumor necrosis factor alpha, and regulated on activation, normal T cells expressed and secreted (RANTES) increased in response to RV infection in Df mice, but not in PBS mice (P<0.05). The level of IL-10 significantly decreased following RV infection in Df mice (P<0.05). Conclusion: Our findings suggest that the augmented induction of proinflammatory cytokines, Th2 cytokines, and chemokines that mediate an eosinophil response and the decreased induction of regulatory cytokines after RV infection may be important manifestations leading to airway inflammation with eosinophil infiltration and changes in airway responsiveness in the asthma model.

• 동의생리병리학회지
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• 제20권6호
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• pp.1593-1597
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• 2006

We hope to evaluate the effects of Gami-Choakwiyeum (GCKY) on the PPAR-${\gamma}$’ in the OVA induced asthma mouse model. Female BALB/c mice, 8 weeks of age and free of murine specific pathogens were used. Mice were sensitized by intraperitoneal injection of OVA emulsified in aluminum hydroxide in a total volume of 200 ${\mu}{\ell}$ on one day and 14 days. On 21, 22, and 23 days after the initial intraperitoneal injection of OVA, the mice were challenged using an ultrasonic nebulizer. GCKY was administered 7 times by oral gavage at 24 hour intervals fromdays 19 after intraperitoneal injection of OVA. Bronchoalveolar lavage was perfromed 72 hours after the last challenge, and total cell numbers in the BAL fluid were counted. Also, the level of PPAR-${\gamma}$ of normal and OVA-induced asthma moused with/without administration of GCKY were measured by Western blot analysis. For the histologic examination, the specimens were stained with hematoxylin 2 and eosin-Y.(H & E). Numbers of total cells were increased significantly at 72 h after OVA inhalation compared with numbers of total cells in the normal and the administration of GCKY. Especially, the increased numbers of eosinophils in BAL fluids after OVA inhalation were significantly increased. However, the numbers of eosinophils reduced by the administration of GCKY. Western blot analysis revealed that PPAR-${\gamma}$ levels in nuclear level were increased slightly after OVA inhalation compared with the levels in the normal group. After the administration of GCKY, PPAR-${\gamma}$ levels in cytosolic and nuclear levels at 72 h after OVA inhalation were markedly increased. On pathologic examination, there were many acute inflammatory cells around the alveoli, bronchioles, and airway lumen of mice with OVA-induced asthma compared with inflammatory cells in the normal group. However, acute inflammatory cells around alveoli, bronchioles, and airway lumen markedly decreased after administration of GCKY, GCKY can increase a PPAR-${\gamma}$ level and could be an effective treatment in asthma patients through the PPAR-${\gamma}$ mechanism for bronchial 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.

• 생명과학회지
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• 제17권3호통권83호
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• pp.396-401
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• 2007

천식이 유발된 Balb/c마우스와 동일한 조건의 IL-10 KO 마우스에 천식의 원인으로 알려진 DEP와 지하철역내에서 채집한 PM (10 ${\mu}g/m^3$)을 inhalation chamber,에 넣고 하루 4시간씩 흡입시킨 후 시료들을 채취하여 ICAM-1, VCAM-1의발현을 살펴 천식증상의 악화에 DEP와 PM이 어데한 영향을 미치는지 확인하였다. 본 실험의 결과 천식이 유발된 일반 Balb/c 마우스에 있어서는 DEP와 PM의 노출에 의하여 ICAM-1 및 VCAM-1의 발현이 세기관지 주위 조직들에서 미약하게 증가하였다. 그러나 IL-10 KO 마우스의 경우 DEP와 PM을 노출시켰을 때 ICAM-1 및 VCAM-1의 발현이 아주 강하게 증가하였다. 따라서, 본 결과는 IL-10에 대한 항체요법이 천식증상의 완화에 쓰일 수 있는 가능성을 암시하며, 한편 자동차 배기가스와 지하철 미세분진의 발생을 예방할 경우 천식과 관련한 세기관지의 염증을 완화시킬 수 있음을 간접적으로 증명한 것이라 할 수 있다.

• BMB Reports
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• 제48권3호
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• pp.178-183
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• 2015

Dendritic cells play an important role in determining whether na${\ddot{i}}$ve T cells mature into either Th1 or Th2 cells. We determined whether heat-shock protein X (HspX) purified from Mycobacterium tuberculosis regulates the Th1/Th2 immune response in an ovalbumin (OVA)-induced murine model of asthma. HspX increased interferon-gamma, IL-17A, -12 and transforming growth factor (TGF)-${\beta}$ production and T-bet gene expression but reduced IL-13 production and GATA-3 gene expression. HspX also inhibited asthmatic reactions as demonstrated by an increase in the number of eosinophils in bronchoalveolar lavage fluid, inflammatory cell infiltration in lung tissues, airway luminal narrowing, and airway hyper-responsiveness. Furthermore, HspX enhanced OVA-induced decrease of regulatory T cells in the mediastinal lymph nodes. This study provides evidence that HspX plays critical roles in the amelioration of asthmatic inflammation in mice. These findings provide new insights into the immunotherapeutic role of HspX with respect to its effects on a murine model of asthma.