• 제목/요약/키워드: Airway hyperresponsiveness

검색결과 99건 처리시간 0.026초

Magnolol exerts anti-asthmatic effects by regulating Janus kinase-signal transduction and activation of transcription and Notch signaling pathways and modulating Th1/Th2/Th17 cytokines in ovalbumin-sensitized asthmatic mice

  • Huang, Qi;Han, Lele;Lv, Rong;Ling, Ling
    • The Korean Journal of Physiology and Pharmacology
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    • 제23권4호
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    • pp.251-261
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    • 2019
  • Allergic asthma, is a common chronic inflammatory disease of the airway presenting with airway hyperresponsiveness and airway remodelling. T helper cells-derived cytokines are critically associated with asthma pathogenesis. Janus kinase-signal transduction and activation of transcription (JAK/STAT) signaling is found to be involved in asthma. Magnolol is a plant-derived bioactive compound with several pharmacological effects. The study aimed to assess the effects of magnolol in ovalbumin (OVA)-induced asthmatic model. BALB/c mice were sensitized and challenged with OVA. Magnolol (12.5, 25, or 50 mg/kg body weight) was administered to separate groups of animals. Dexamethasone was used as the positive control. Cellular infiltration into the bronchoalveolar lavage fluid (BALF) were reduced on magnolol treatment. The levels of Th2 and Th17 cytokines were reduced with noticeably raised levels of interferon gamma. Lung function was improved effectively along with restoration of bronchial tissue architecture. OVA-specific immunoglobulin E levels in serum and BALF were decreased by magnolol. Magnolol reduced Th17 cell population and effectively modulated the JAK-STAT and Notch 1 signaling. The results suggest the promising use of magnolol in therapy for allergic asthma.

운동유발성 기관지수축의 정도와 Methacholine 유발시험의 민감도 및 최대기도협착과의 관련성 (Correlation of Exercise-Induced Bronchoconstriction to $PC_{20}$ and Maximal Airway Narrowing on the Dose-Response Curve to Methacholine)

  • 임형석;윤경애;고영률
    • Tuberculosis and Respiratory Diseases
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    • 제42권2호
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    • pp.165-174
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    • 1995
  • 연구배경: 운동유발성 천식은 운동에 의해서 기관지 수축이 나타나는 것으로, 일상생활에서 흔히 경험하는 천식발작의 형태로서, 특히 소아에서는 중요하다. 이러한 운동유발성 기관지 수축은 비특이적으로 발생된다는 점에서, 통상적으로 측정, 평가되는 histamine이나 metacholine에 의한 비특이적 기관지 반응도와 밀접한 관련을 생각할 수 있다. 비특이적 기관지 반응도 중 $PC_{20}$으로 표시되는 기도 민감도는 운동유발성 기관지 수축의 정도와 비례하는 것이 밝혀져 있으나, 또 다른 요소인 최대 기도 협착의 정도와 운동유발성 기관지 수축(EIB)의 정도와의 연관성에 대해서는 연구된 바 없다. 방법: 56명의 천식 환아에서 고농도의 methacholine 유발시험에서의 $PC_{20}$, 최대반응고원(MRP), 최대기도 협착(MAN)을 측정하고, 운동유발시험에서의 운동유발성 기관지수축을 측정하였다. 이들을 운동유발성 기관지 수축의 정도에 따라 3군으로 구분하여, 각군간의 $PC_{20}$, MRP, MAN의 차이를 알아보고 전체 대상에서 운동유발성 기관지 수축의 정도와 $PC_{20}$, MRP, MAN 각각과의 상관관계를 알아보았다. 결과: 1) 운동유발성 기관지 수축이 20% 이상인(+) EIB군의 $PC_{20}$은, 10% 이하인 (-)EIB의 $PC_{20}$보다 유의하게 낮았다(p<0.01). 2) 전체 대상에서 methacholine $PC_{20}$의 log치는 운동유발성 기관지수축의 정도와 유의한 역비례 관계를 나타내었다(r=-0.568, p<0.01). 3) 전체 56명중 36명에서 MRP를 구할수 있었는데 이들에서 MRP와 운동유발성 기관지 수축의 정도는 유의한 상관관계를 보였다(r=0.355, p<0.05). 4) (+)EIB인 군의 MAN은 (-)EIB군의 MAN보다 유의하게 높았다. 5) 전체 대상에서 MAN은 운동유발성 기관지 수축의 정도와 유의한 정비례 관계를 나타내었다(r=0.546, p<0.01). 결론: 운동유발성 기관지 수축의 정도는 methacholine유발검사로 측정된 $PC_{20}$과 뿐만 아니라 MAN의 정도와 유의한 상관관계를 나타내었다. 이같은 결과는 비록 특이적 기관지 반응도를 결정하는 2가지 요소가, 비록 서로 다른 기전이지만, 운동에 대한 반응을 결정하는 요인으로 중요하게 작용함을 암시한다. 또한 NSBR을 평가할때 $PC_{20}$뿐만 아니라 MRP혹은 MAN의 측정이 가능한 포함되어야 할것이다.

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만성 기침 환자에서 기관지와 흉곽외 기도의 Methacholine 유발검사의 의의 (Methacholine Responsiveness of Bronchial and Extrathoracic Airway in Patients with Chronic Cough)

  • 심재정;김제형;이승룡;권영환;이소라;이상엽;이상화;서정경;조재연;인광호;유세화;강경호
    • Tuberculosis and Respiratory Diseases
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    • 제44권4호
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    • pp.853-860
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    • 1997
  • 연구배경 : 만성 기침은 임상에서 흔한 증상으로 대부분은 후비루증(posterior nasal dripping : PND), 천식, 위식도 역류증, 기관지염 등으로 인한 것으로 알려져 있다. 만성 기침 환자 중 일부분은 기침과 동반하여 천명이나, 호흡곤란 등과 같은 기관지 천식과 유사한 증상을 경우가 많아 기관지 과민반응 검사를 시행하게 된다. 기관지 과민반응 검사는 대부분 $FEV_1$을 측정하지만 흉곽외 기도의 과민반응은 측정하지 못하는 단점이 있다. 본 연구는 만성 기침 환자를 대상으로 기관지와 흉부외 기도의 methacholine 유발 검사를 시행하여 기도 과민 반응을 평가하여 상관 관계를 알아보고자 본 연구를 시행하였다. 대상 및 방법 : 대상 환자는 2개월 이상 기침이 있는 111명의 환자를 대상으로 하였으며, 남자 55명, 여자 56명으로 평균 연령은 $37.4{\pm}13.0$세였다. 대상 환자는 심혈관 질환, 전신 질환 등이 없었으며, 과거에 기관지 진단 받은 병력이 없고 기관지 확장제나 사용한 병력이 없었던 환자였다. 기침이나 천명 또는 간헐적인 호흡곤란 등의 증상은 문진으로 확인하였고, 기침만 존재한 환자 46명, 기침과 천명이 있는 환자 24명, 기침과 호흡곤란이 있는 환자 22명, 기침, 천명 및 호흡곤란이 있는 환자 19명이었다. 대상환자의 폐기능검사는 $FEV_1$(%) $106.5{\pm}15.3$, FVC(%) $100.1{\pm}12.8$, $FEV_1$/FVC(%) $106.3{\pm}13.1$로 정상이었다. Methacholine 유발검사는 0.0625 에서 25 mg/ml의 2배수 농도를 흡입한 5분후 기관지 과민 반응은 $PC_{20}FEV_1$으로 측정하였고, 흉곽외 기도 과민 반응은 최대 중간흡입 기류속도인 $MIF_{50}$으로 측정하여 연속 3회 감소하고 25%이상 감소한 $PC_{25}MIF_{50}$으로 측정하여 25mg/ml 이하의 농도에서 양성인 경우를 기관지(BHR) 및 흉부외 기도(EAHR) 에 각각 반응이 있다고 판독하여 대상 환자의 상관 관계를 확인하여 다음과 같은 결과를 얻었다. 결 과 : 대상 환자 총 111명중에 기관지 과민반응(BHR)이 27명, 흉곽외 기도 과민반응(EAHR)이 16명, BHR과 EAHR이 함께 있는 환자 8명으로 과민 반응이 있는 환자는 총 50명이었으며, 그외의 61명은 기관지와 흉부외 기도의 과민반응이 없었다. BHR 또는 EAHR이 양성인 환자 50명중에 기침만 있는 환자는 BHR이 3명, EAHR이 9명, BER과 EAHR이 같이 있는 환자는 2명으로 EAHR이 가장 많았으며, 기침과 천명이 있는 환자는 BHR이 10명, EAHR이 2명 및 BHR과 EAHR이 같이 있는 환자는 2명으로 BHR이 가장 많았고, 기침과 호흡곤란이 있는 환자는 BHR이 7명, EAHR이 3명, BHR과 EAHR이 같이 있는 환자는 1명으로 BHR이 가장 많았다. 기침, 천명 및 호흡곤란이 모두 있는 환자는 BHR이 7명, EAHR이 2명, BHR과 EAHR이 같이 있는 환자는 3명으로 BHR이 가장 많았다. BHR와 EAHR이 모두 음성인 환자는 총 61명이었으며, 기침만 있는 환장 32명, 기침과 천명이 있는 환자 10명, 기침과 호흡곤란이 있는 환자 11명, 기침, 천명 및 호흡곤란이 모 두 있는 환자는 7명이었다. 결 론 : Methacholine에 양성 반응인 환자중 호흡곤란이나 천명이 동반된 만성 기침환자에서는 주로 기관지 과민 반응이 나타났으며, 기침 단독 증상인 환자에서는 반응이 존재함을 알 수 있었다.

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Airway Smooth Muscle Sensitivity to Methacholine in Precision-Cut Lung Slices (PCLS) from Ovalbumin-induced Asthmatic Mice

  • Kim, Hae Jin;Kim, Yeryung;Park, Su Jung;Bae, Boram;Kang, Hye-Ryun;Cho, Sang-Heon;Yoo, Hae Young;Nam, Joo Hyun;Kim, Woo Kyung;Kim, Sung Joon
    • The Korean Journal of Physiology and Pharmacology
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    • 제19권1호
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    • pp.65-71
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    • 2015
  • Asthma is a chronic inflammatory disease characterized by airway hyperresponsiveness (AHR) and reversible airway obstruction. Methacholine (MCh) is widely used in broncho-provocation test to evaluate airway resistance. For experimental investigation, ovalbumin-induced sensitization is frequently used in rodents (Ova-asthma). However, albeit the inflammatory histology and AHR in vivo, it remains unclear whether the MCh sensitivity of airway smooth muscle isolated from Ova-asthma is persistently changed. In this study, the contractions of airways in precision-cut lung slices (PCLS) from control, Ova-asthma, and IL-13 overexpressed transgenic mice (IL-13TG) were compared by analyzing the airway lumen space (AW). The airway resistance in vivo was measured using plethysmograph. AHR and increased inflammatory cells in BAL fluid were confirmed in Ova-asthma and IL-13TG mice. In the PCLS from all three groups, MCh concentration-dependent narrowing of airway lumen (${\Delta}AW$) was observed. In contrast to the AHR in vivo, the $EC_{50}$ of MCh for ${\Delta}AW$ from Ova-asthma and IL-13TG were not different from control, indicating unchanged sensitivity to MCh. Although the AW recovery upon MCh-washout showed sluggish tendency in Ova-asthma, the change was also statistically insignificant. Membrane depolarization-induced ${\Delta}AW$ by 60 mM $K^+$ (60K-contraction) was larger in IL-13TG than control, whereas 60K-contraction of Ova-asthma was unaffected. Furthermore, serotonin-induced ${\Delta}AW$ of Ova-asthma was smaller than control and IL-13TG. Taken together, the AHR in Ova-asthma and IL-13TG are not reflected in the contractility of isolated airways from PCLS. The AHR of the model animals seems to require intrinsic agonists or inflammatory microenvironment that is washable during tissue preparation.

Phellinus linteus Extract Exerts Anti-asthmatic Effects by Suppressing NF-${\kappa}B$ and p38 MAPK Activity in an OVA-induced Mouse Model of Asthma

  • Yan, Guang Hai;Choi, Yun Ho
    • IMMUNE NETWORK
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    • 제14권2호
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    • pp.107-115
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    • 2014
  • Phellinus linteus has been used as a traditional herbal medicine in Asian countries and is known to have anti-tumor, immunomodulatory, anti-inflammatory, and anti-allergic activities. However, the protective effects of P. linteus against experimental asthma have not been fully investigated. The objective of this study was to determine whether P. linteus ethanol extract (PLE) suppresses inflammatory response in an OVA-induced asthma model. As expected, the oral administration of PLE significantly inhibited eosinophilic airway inflammation and airway hyperresponsiveness in OVA-challenged BALB/c mice. Supporting these data, the augmentation of Th2 cytokines (IL-4, IL-5, and IL-13), eotaxin, and adhesion molecules in lung tissues and bronchoalveolar lavage fluid after OVA inhalation was markedly attenuated by PLE. Furthermore, PLE reduced OVA-induced activation of NF-${\kappa}B$ and p38 MAPK in lung tissues. Therefore, our results suggest the potential of P. linteus as a therapeutic agent for asthma.

소청룡탕 효능에 관한 기초 실험 연구 문헌 분석 (Analysis of Biological Experiment on Socheongryong-tang (Xiaoqinglong-tang))

  • 김정훈;신현규
    • 대한한의학회지
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    • 제33권3호
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    • pp.54-73
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    • 2012
  • Objectives: To investigate the scientific evidence of Korean Medicine (KM), papers on Socheongryong-tang (Xiaoqinglong-tang), which is frequently used in medical clinics or hospitals of Korean medicine, were collected and analyzed. Methods: Papers were classified by the registration of domestic or international journals, the year of publication, experimental models and the subjects of biological activities. The mechanisms of biological activity in accordance with therapeutic effects of Socheongryong-tang (Xiaoqinglong-tang) were noted. Results: Among 98 papers included, 21 were published in domestic journals whereas 35 were in Chinese journals and 43 in Japanese journals. Most reported biological activities were amelioration of asthma. Socheongryong-tang (Xiaoqinglong-tang) regulated interleukin and interferon and immunoglobulin, inhibited the production of nerve growth factor, endotheliln-1, nitric oxide, toll-like receptor-4, p-Akt and increased extracellular signal regulated kinase and cyclin D1, which led to decreased bronchi inflammation and bronchoconstriction, and inhibited the proliferation of airway smooth muscle cells, mucus secretion and airway hyperresponsiveness. In addition, Socheongryong-tang (Xiaoqinglong-tang) also restored tissues injured by asthma so that respiratory function recovered. Conclusions: Amelioration of asthma by Socheongryong-tang (Xiaoqinglong-tang) is supported by objective and scientific evidence.

생쥐에서 급성 폐렴에 대한 여정자 열매 추출물의 억제효과 (Ligustrum lucidum Fruits Extract Inhibits Acute Pulmonary Inflammation in Mice)

  • 곽호근;임흥빈
    • 한국약용작물학회지
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    • 제21권5호
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    • pp.323-328
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    • 2013
  • Traditionally, Ligustrum lucidum fruits (LL) is one of the well-known oriental herb used in the treatment of skin and lung inflammation. This study investigated anti-inflammatory effects of LL in the pathogenesis of acute pulmonary inflammation in mice. Acute pulmonary inflammation was induced by intratracheal instillation of cigarette smoke condensate (CSC) and lipopolysaccharide (LPS) 5 times within 12 days in mice. LL extract was administered orally at a dose of 50 or 200 mg/kg. Administration of LPS and CSC significantly elevated airway hyperresponsiveness (AHR) to mice, and increased in the levels of inflammatory cells and mediators in mice. However, the LL extract significantly reduced the elevated AHR, and the increase of neutrophils, $CD4^+/CD3^+$ cells and $CD8^+/CD3^+$ cells, along with reducing the expression of TNF-${\alpha}$, IL-6, and MIP-2. Moreover, the LL extract alleviated the infiltration of inflammatory cells in expanded airway walls histologically. These results indicate that the LL extract has an inhibitory effects on acute pulmonary inflammation and AHR in murine model, and plays a crucial role as a immunomodulator which possess anti-inflammatory property.

Inhibitory effects of synthetic isoflavone compounds on IL-5 bioactivity

  • Ju, Jung-Hun;Jung, Sang-Hun;Cho, Soo-Hyun;Dang, The-Hung;Lee, Jee-Hyun;Kim, Mi-Kyeong;Lee, Seung-Ho;Ryu, Jae-Chun;Min, Kyung-Rak
    • 대한약학회:학술대회논문집
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    • 대한약학회 2003년도 Proceedings of the Convention of the Pharmaceutical Society of Korea Vol.1
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    • pp.210.2-211
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    • 2003
  • Eosinophilic inflammation is the main histological correlate of airway hyperresponsiveness and tissue injury in the pathogenesis of bronchial asthma. Interleukin (IL)-5 appears to be one of main proinflammatory mediators that induce eosinophilic inflammation. Allergic IL -5-deficient mice do not generate eosinophilia in the bone marrow, blood or lung in response to allergen provocation. (omitted)

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Selonsertib, an ASK1 Inhibitor, Ameliorates Ovalbumin-Induced Allergic Asthma during Challenge and Sensitization Periods

  • So-Young Han;Dong-Soon Im
    • Biomolecules & Therapeutics
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    • 제32권4호
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    • pp.451-459
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    • 2024
  • Apoptosis signal-regulating kinase 1 (ASK1) is an upstream signaling molecule in oxidative stress-induced responses. Because oxidative stress is involved in asthma pathogenesis, ASK1 gene deficiency was investigated in animal models of allergic asthma. However, there is no study to investigate whether ASK1 inhibitors could be applied for asthma to date. Selonsertib, a potent and selective ASK1 inhibitor, was applied to BALB/c mice of an ovalbumin (OVA)-induced allergic asthma model. Selonsertib suppressed antigen-induced degranulation of RBL-2H3 mast cells in a concentration-dependent manner. The administration of selonsertib both before OVA sensitization and OVA challenge significantly reduced airway hyperresponsiveness, and suppressed eosinophil numbers and inflammatory cytokine levels in the bronchoalveolar lavage fluid. Histopathologic examination elucidated less inflammatory responses and reduced mucin-producing cells around the peribronchial regions of the lungs. Selonsertib also suppressed the IgE levels in serum and the protein levels of IL-13 in the bronchoalveolar lavage fluid. These results suggest that selonsertib may ameliorate allergic asthma by suppressing immune responses and be applicable to allergic asthma.

Increased B cell-activating factor (BAFF) level in the sputum of children with asthma

  • Jee, Hye-Mi;Choi, Bong-Seok;Kim, Kyung-Won;Sohn, Myung-Hyun;Han, Man-Yong;Kim, Kyu-Earn
    • Clinical and Experimental Pediatrics
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    • 제53권8호
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    • pp.795-800
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    • 2010
  • Purpose: B cell-activating factor (BAFF) is a tumor-necrosis factor (TNF) superfamily member best known for its role in the survival and maturation of B cells. BAFF activity is observed in naive cells as well as in effector/memory T cells. We aimed to explore whether BAFF in sputum is expressed at elevated levels in asthmatic airways and associated with eosinophilic inflammation, pulmonary function, and bronchial hyperresponsiveness in children. Methods: One hundred and fifty-four asthmatic children and 98 healthy children were enrolled in the study. Sputum supernatants were collected and sputum BAFF and eosinophil cationic protein (ECP) levels were measured. We performed pulmonary function tests and methacholine challenge tests, while measuring total eosinophil count, total serum IgE, and serum ECP in all subjects. Results: Asthmatic children had significantly higher levels of BAFF in induced sputum [26.50 (10.50-100.27) pg/mL] compared to healthy children [18.32 (7.68-44.63) pg/mL; $P$=0.011]. Sputum BAFF positively correlated with sputum eosinophils (${\gamma}$=0.406, $P$<0.001) and sputum ECP (${\gamma}$=0.789, $P$<0.001). Significant negative correlations were found between sputum BAFF and FEV1 (${\gamma}$=-0.291, $P$<0.001) or post-bronchodilator FEV1 (${\gamma}$=-0.334, $P$<0.001), whereas nonsignificant correlations were found between sputum BAFF and bronchial hyperresponsiveness, serum eosinophil count, and serum ECP. Conclusion: These findings suggest that BAFF may play a role in childhood asthma, and BAFF levels in sputum could be a supportive marker that represents airway inflammation, especially eosinophilic inflammation.