• 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.

• 한국약용작물학회지
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• 제20권2호
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• pp.129-135
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• 2012

The feature of asthma are airway inflammation (AI), reversible airway obstruction, and an increased sensitivity to bronchoconstricting agents, elevated airway hyperresponsiveness (AHR), excess production of Th2 cytokines, and eosinophil accumulation in the lungs. This study was performed to investigate if oral administration of $Scutellaria$ $baicalensis$ Georgi water extracts (SBG) have the antiasthmatic potential for the treatment of asthma. Asthmatic HI and AHR were induced by systemic sensitization to ovalbumin (OVA) with intratracheal instillation with 0.1 mg/mL of diesel exhaust particles (DEP) suspension once a week for 10 weeks in BALB/c mice. SBG was orally administered with the concentraion of 200 mg/kg 5 days a week for 10 weeks. Long-term SBG treatment suppressed the eosinophil infiltration into airways from blood, the asthmatic AI and AHR by attenuating the production of cytokine IL-4, IL-5 and IL-13, histamine and OVA-specific IgE. Our data suggest that SBG has inhibitory effects on AI and AHR in a mouse model of asthma, may act as a potential Th2 cytokine antagonist, and may have a therapeutic effect on allergic asthma.

• 한방안이비인후피부과학회지
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• 제20권1호통권32호
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• pp.177-194
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• 2007

Fructus of Rubus coreanus $M_{IQ.}$. (FRCM) has been used for stuttering urination, prostate gland disease, and impotence in Korean traditional medicine. Water extract of FRCM (WFRCM) treatment significantly attenuated airway hyperreactivity (AHR). Airway recruitment of leukocytes and eosinophils was also markedly reduced by WFRCM administration, suggesting that WFRCM can alleviate the airway inflammation. However, the level of cytokine (IL-4, IL-5, and IL-13) in bronchoalveolar lavage fluid (BALF) and lung was not different compared with positive control. WFRCM reduced the number of draining lymph node cells during OVA-induced allergic asthma. I further examined transcription level of cytokine in lung. WFRCM treatment reduced IL-4 and IL-13 mRNA in lung and inhibited IgE and IgG1 but not IgG2a. My data suggest that WFRCM attenuates OVA-induced allergic asthma through inhibition of Th2 cell response.

• Tuberculosis and Respiratory Diseases
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• 제48권1호
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• pp.33-44
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• 2000

연구배경: 기관지천식은 기도의 과민성을 특징을 지닌 기도의 염증성 질환이며, 기관지천식에서의 기도 염종의 특성에 관한 연구는 기관지천식의 병인과 병태생리를 이해하는데 필수적이다. 본 연구의 목적은 백서에서 국내에서 개발된 일실 체용적 변동기록기을 이용하여 항원에 의한 반응을 관찰하여 기관지천식의 모델을 확립하고, 사람 기관지 천식과의 유사성을 알아보고자 백서의 기관지천식 모텔에서 기도의 염증을 관찰하여 항원에 의한 기도의 반응 양상에 따른 차이를 비교하고자 하였다. 대상 및 방법: 백서 30마리에 0.1mg의 난황을 피하로 주입하여 감작시키고, 감작후 14-16일 항원유발시험을 시행하여 각 10마리씩 3군으로 나누어 기도의 반응을 관찰하면서 1시간, 6-8시간, 24시간 후에 사망시켜 폐조직의 변화를 관찰하였다. 대조군 10마리는 감작군과 동일한 방법으로 항원을 흡입하고 1일 후에 사망시켰다. 기도반응은 동물용 일실 체용적 변동기록기를 사용하여 enhanced pause(Penh)를 지표로 측정하였다. 병리소견은 백서를 사망시켜 폐와 기관지를 절제한 후 Hematoxylin Eosin으로 염색하여 기관, 대기관지 및 소기관지 및 혈관주위에서 염증반응과 호산구 침윤을 관찰하였다. 결 과: 항원 유발시험을 시행한 20마리중 총 17마리(85%)에서 항원에 의한 기도의 수축반응을 보였다. 이들중 15 마리(75%)에서 조기반응을, 5 마리(25%)는 이중반응을 보였고 2마리(10%)는 후기반응만을 보였다. 항원 유발 후 기관, 대기관지, 소기관지와 혈관주 위에서의 염증반응은 1시간군, 6시간군, 1일군모두에서 대조군과 유의한 차이는 없었다(p>0.05). 항원유발시험후 호산구의 침윤은 1시간군과 대조군에서는 호산구의 침윤을 전혀 관찰할 수 없었으나, 6시간군은 5마리(50%)에서 호산구의 침윤을 관찰하였으며, 대조군과 유의한 호산구의 침윤을 관찰할 수 있었다(p<0.05). 조기반응과 후기반응을 관찰할 수 있었던 6시간군과 1일군에서 조기반응군(조기반응만을 보인 백서, n=10)과 후기반응군(이중반응과 후기반응만을 보인 백서, n=7) 에서 염증의 침윤은 모든 부위에서 유의한 차이는 없었다. 호산구의 침윤은 조기반응군에는 10마리중 4마리(40%)에서 $0.7{\pm}1.1$등급이었으며, 후기반응군은 7마리중 4 마리(57.1%)에서 $1.0{\pm}1.0$으로 높았으나, 통계적으로 유의하지는 않았다(p>0.05). 결 론: 백서의 기관지천식 모델에서 항원에 의한 기도의 수축 반응은 높고 반응률을 보였으나 기도의 염증 반응을 유발하지는 않으며, 호산구의 침윤도 미약하다고 생각된다. 그러므로 백서 기관지 천식모델은 항원에 의한 기도 반응의 연구에는 좋으나, 사랑의 만성 기관지 천식을 연구하기에는 적당치 못하다고 생각된다.

• 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.

• Tuberculosis and Respiratory Diseases
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• 제78권1호
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• pp.8-17
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• 2015

Background: AMP-activated protein kinase (AMPK) not only functions as an intracellular energy sensor and regulator, but is also a general sensor of oxidative stress. Furthermore, there is recent evidence that it participates in limiting acute inflammatory reactions, apoptosis and cellular senescence. Thus, it may oppose the development of chronic obstructive pulmonary disease. Methods: To investigate the role of AMPK in cigarette smoke-induced lung inflammation and emphysema we first compared cigarette smoking and polyinosinic-polycytidylic acid [poly(I:C)]-induced lung inflammation and emphysema in $AMPK{\alpha}1$-deficient ($AMPK{\alpha}1$-HT) mice and wild-type mice of the same genetic background. We then investigated the role of AMPK in the induction of interleukin-8 (IL-8) by cigarette smoke extract (CSE) in A549 cells. Results: Cigarette smoking and poly(I:C)-induced lung inflammation and emphysema were elevated in $AMPK{\alpha}1$-HT compared to wild-type mice. CSE increased AMPK activation in a CSE concentration- and time-dependent manner. 5-Aminoimidazole-4-carboxamide-1-${\beta}$-4-ribofuranoside (AICAR), an AMPK activator, decreased CSE-induced IL-8 production while Compound C, an AMPK inhibitor, increased it, as did pretreatment with an $AMPK{\alpha}1$-specific small interfering RNA. Conclusion: $AMPK{\alpha}1$-deficient mice have increased susceptibility to lung inflammation and emphysema when exposed to cigarette smoke, and AMPK appears to reduce lung inflammation and emphysema by lowering IL-8 production.

• Toxicological Research
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• 제30권1호
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• pp.13-18
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• 2014

Electronic cigarettes (e-cigarettes) are becoming increasingly popular worldwide and their cellular effects warrant further evaluation. In this study, we investigated the effects of an e-cigarette cartridge solution on allergen related asthmatic airway inflammation (AI) and airway hyperresponsiveness (AHR), when it is delivered by intratracheal route in mice. Asthmatic AI and AHR were induced by systemic sensitization to ovalbumin (OVA) followed by intratracheal, intraperitoneal, and aerosol allergen challenges in BALB/c mice. The cartridge solution of e-cigarette (containing 16 mg/ml nicotine) was diluted 50 times and $100{\mu}l$ of the diluted solution was intratracheally instilled to OVA-sensitized (OVA-S) mice two times a week for 10 weeks. Long-term e-cigarette inhalation elicited no remarkable changes in the activities of alanine aminotransferase (ALT), aspartate aminotransferase (AST), lactate dehydrogenase enzymes in serum, however, increased infiltration of inflammatory cells including eosinophils, into airways from blood, aggravated the asthmatic AI and AHR, and stimulated the production of cytokines such as interleukin (IL)-4, IL-5 and IL-13, and OVA-specific IgE production. Our data suggest that the inhalation of e-cigarette solutions can function as an important factor to exacerbate the allergy-induced asthma symptoms. Further studies are needed to address the effects of e-cigarette solutions on human health.

• Parasites, Hosts and Diseases
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• 제60권4호
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• pp.229-239
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• 2022

The high percentage of Vermamoeba was found in tap water in Korea. This study investigated whether Vermamoeba induced allergic airway inflammation in mice. We selected 2 free-living amoebas (FLAs) isolated from tap water, which included Korean FLA 5 (KFA5; Vermamoeba vermiformis) and 21 (an homolog of Acanthamoeba lugdunensis KA/E2). We axenically cultured KFA5 and KFA21. We applied approximately 1×10⁶ to mice's nasal passages 6 times and investigated their pathogenicity. The airway resistance value was significantly increased after KFA5 and KFA21 treatments. The eosinophil recruitment and goblet cell hyperplasia were concomitantly observed in bronchial alveolar lavage (BAL) fluid and lung tissue in mice infected with KFA5 and KFA21. These infections also activated the Th2-related interleukin 25, thymic stromal lymphopoietin, and thymus and activation-regulated chemokines gene expression in mouse lung epithelial cells. The CD4⁺ interleukin 4⁺ cell population was increased in the lung, and the secretion of Th2-, Th17-, and Th1-associated cytokines were upregulated during KFA5 and KFA21 infection in the spleen, lung-draining lymph nodes, and BAL fluid. The pathogenicity (allergenicity) of KFA5 and KFA21 might not have drastically changed during the long-term in vitro culture. Our results suggested that Vermamoeba could elicit allergic airway inflammation and may be an airway allergen.

• IMMUNE NETWORK
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• 제22권6호
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• pp.45.1-45.15
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• 2022

Asthma is a chronic airway inflammatory disease characterized by reversible airway obstruction and airway hyperreactivity to various environmental stimuli, leading to recurrent cough, dyspnea, and wheezing episodes. Regarding inflammatory mechanisms, type 2/eosinophilic inflammation along with activated mast cells is the major one; however, diverse mechanisms, including structural cells-derived and non-type 2/neutrophilic inflammations are involved, presenting heterogenous phenotypes. Although most asthmatic patients could be properly controlled by the guided treatment, patients with severe asthma (SA; classified as a treatment-refractory group) suffer from uncontrolled symptoms with frequent asthma exacerbations even on regular anti-inflammatory medications, raising needs for additional controllers, including biologics that target specific molecules found in asthmatic airway, and achieving the precision medicine for asthma. This review summarizes the immunologic basis of airway inflammatory mechanisms and current biologics for SA in order to address unmet needs for future targets.

• 한국응용약물학회:학술대회논문집
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• 한국응용약물학회 1996년도 춘계학술대회
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• pp.74-79
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• 1996