• Tuberculosis and Respiratory Diseases
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• 제48권6호
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• pp.922-931
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• 2000

배경 및 목적 : 기관지천식의 중요한 특징적인 병인인 기도의 만성염증 상태와 증상의 변화를 판단하는 객관적인 지표로서 여러 가지 방법이 시도되고 있는데 최근에는 비침습적이고 비교적 간단한 유도객담 검사로 침습적인 기관지 조직 검사나 기관지폐포세척술을 대신하려는 경향이 있다. 저자들은 기관지천식 환자의 유도객담에서 호산구, eosinophil cationic protein(ECP), interleukin(IL)-3, IL-5, granulocyte-macrophage colony-stimulating factor(GM-CSF), 그리고, nitric oxide(NO)의 유도체를 측정하고, 객담내 NO 및 호산구와 관계가 있다고 알려진 cytokine들의 농도가 증상 및 기도의 염증상태를 반영하는 지표로서 이용될 수 있는지를 알아보고자 하였다. 방법 : 기관지천식 환자 30명을 대상으로 2주간 경구용 프레드니솔론 30mg을 투여하고, 약제 투여 전후로 1초간 노력성 호기량($FEV_1$과 혈중 총 호산구수, 그리고 유도객담 검사를 시행하여 객담내 호산구 비율과 ECP, IL-3, IL-5, GM-CSF, 그리고, NO 유도체를 측정하였다. 결과 : 대상환자중 남자는 13a여(43.3%), 여자는 17명(56.7%)이었고 연령분포는 19세부터 64세까지였으며 평균연령은 41.8세였다. 30명중 2명은 두 번째 검사시 객담이 채취되지 않았고, 3명은 두 번째 방문을 하지 않았다. 프레드니솔론 투여후 평균 1초당 노력성 호기량(% of predicted value)은 78.1$\pm$27.2%에서 90.3$\pm$18.3%로 개선되었고(P<0.001), 유도객담내 평균 호산구비율은 56.1$\pm$27.2%에서 29.6$\pm$21.3%로 (P<0.001), 객담내 평균 ECP 농도는 $134.5\pm68.1{\mu}\;g/L$에서 $41.5\pm42.4\;{\mu}g/L$로 유의하게 감소하였고(P<0.001), 평균 혈중 총 호산구수는 425.7$\pm$265.9에서 287.7$\pm$294.7로 감소하는 경향을 보였지만 통계적으로 유의하지 않았다. 유도객담내 NO 유도체의 평균 농도는 프레드니솔론 투여 전호로 유의한 차이가 없었으며($70.4\pm44.6\;{\mu}mol/L$ vs $91.5\pm48.3\;{\mu}mol/L$) 평균 eotaxin 농도는 27.7$\pm$12.8 pg/ml에서 21.7$\pm$8.7 pg/ml로 감소하는 경향을 보였다. IL-3, IL-5, CSF는 대부분의 경우에서 측정되지 않았다. 치료전의 1초당 노력성 호기량과 객담내 ECP의 농도 사이에 의미있는 역상관관계가 있었고(r=0.369, P<0.05). 결론 : 유도객담내에서 측정 가능한 여러 인자중 eotaxin 및 ECP가 치료에 따른 기도염증 상태의 변화를 반영하는 지표로 이용될수 있을 것으로 생각된다. 그 외 유도객담내 호산구비율 측정도 치료에 따른 증상이나 염증의 변화를 손쉽게 관찰할수 있는 간단한 방법으로 생각되지만 유도객담에서 Griess reagent를 이용한 NO 유도체의 측정은 기관지천식의 증상이나 염증상태의 변화를 반영하는 지표로서 유용하지 않을 것으로 생각된다.

• 생명과학회지
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• 제20권4호
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• pp.503-510
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• 2010

대부분의 알려진 알러젠들은 단백분해효소의 성격을 가지고 있고 이는 알레르기 반응에서 Th2 면역 반응을 일으키는 데 중요한 역할을 하는 것으로 알려져 있다. 이러한 단백분해효소들과 반응하는 것으로 알려진 protease activated receptor (PAR) 는 4가지 종류가 있으며, 이 중 PAR2의 경우 알레르기 질환과 많은 상관관계를 보여 많은 연구가 되고 있다. 본 연구는 Aspergillus protease 알러젠에 의한 초기 및 만성 Th2 면역반응에서 PAR2 의 역할을 규명하기 위해 Aspergillus protease 알러젠으로 정상쥐와 PAR2 유전자 결핍쥐 모두 Th2 반응을 유도한 후 면역세포의 침윤 정도 및 Th2 관련 cytokine 및 chemokine 유전자들의 발현 정도를 비교하였다. 그 결과 Aspergillus protease 알러젠으로 비강내로 1회 처리했을 경우 중성구의 침윤이 두드러지는데, 이때 PAR2 결핍 마우스는 이러한 면역세포의 침윤이 유의적으로 감소하였다. 또한, 이와 관련된 IL-25, TSLP, Eotaxin 유전자들의 발현 역시 PAR2 결핍 마우스에 현저히 감소하였다. 한편, Aspergillus protease 알러젠으로 비강내로 6회 처리했을 경우 중성구 대신 호산구의 침윤이 두드러지지만 PAR2 결핍 마우스에서 그 정도가 유의적으로 낮았다. OVA 특이 IgE와 IgG1 농도 역시 현저하게 PAR2 결핍 마우스에서 낮았고, CCL21의 발현이 PAR2 결핍마우스 MEF cells에서 현저히 감소하였다. Th2 초기 면역반응에서 가장 중요한 IL-25의 발현에 MAKP p38 pathway가 관여한다는 것을 이번 연구에서 알 수 있다. 본 연구를 통해 Aspergillus protease 알러젠으로 유도된 알러지성 기관지 염증 반응에서 초기 반응뿐만 아니라 만성반응에서도 PAR2가 중요한 것을 알 수 있다.

• 대한한방내과학회지
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• 제41권4호
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• pp.583-598
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• 2020

Objective: The aims of this study were to analyze deficiency-excess pattern identification and to compare the blood cytokines in patients with asthma. Methods: A total of 112 patients with asthma who met the inclusion and exclusion criteria were divided into deficiency syndrome and excess syndrome groups. Blood was examined for eotaxin, interleukin (IL)-1β, IL-4, IL-5, IL-6, IL-13, and tumor necrosis factor (TNF)-α. The Quality of Life Questionnaire for Adult Korean Asthmatics (QLQAKA), a Visual Analogue Scale (VAS), and heart rate variability (HRV) tests were administered to both groups. Results: Pattern identification divided the 112 patients into two categories: a deficiency syndrome group (N=52) and an excess syndrome group (N=60). Analysis of blood cytokines showed higher levels of IL-4, IL-5, and IL-13 in the deficient pattern than in the excess pattern group, but the difference was not statistically significant. Analysis of the HRV revealed a significantly higher mean value for the very-low-frequency (VLF) and high-frequency (HF) bands in the deficiency than in the excess syndrome group. The morbidity duration was longer in the deficiency than in the excess syndrome group, but the difference was not statistically significant. Analysis of the QLQAKA and VAS scores showed a negative correlation, whereas BMI and VAS showed a positive correlation. Conclusions: Levels of blood cytokines, including eotaxin, IL-1β, IL-4, IL-5, IL-6, IL-13, and TNF-α, did not differ statistically between the deficiency and excess syndrome groups. The development of a more accurate asthma-specific pattern identification tool would be useful in asthma control.

• Journal of Microbiology and Biotechnology
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• 제14권4호
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• pp.722-729
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• 2004

Leptin is an adipocyte-secreted hormone and its plasma levels correlate with total body fat mass, however, it also plays a regulatory role in immunity, inflammation, and hematopoiesis. Chemokine is known as a chemoattractant cytokine in inflammatory reaction, but its role in leptin reaction has not been well studied. In this study, the direct effect of leptin on the expression of chemokine mRNAs and lipopolysaccharide (LPS)-induced chemokine KC mRNA in mouse peritoneal macrophages was investigated. Leptin did not induce the expression of lymphotactin, RANTES, eotaxin, MIP-1$\beta$, MIP-1$\alpha$, MIP-2, MCP-1, IP-10, TCA-3, and KC mRNA in mouse peritoneal macrophages, and had no direct effect on the expression of these LPS-induced chemokine mRNAs except KC mRNA. The synergistic effect of leptin on the expression of LPS-induced KC mRNA occurred late in the time course of response to LPS. The increased expressions of Ob-Rb mRNA and leptin receptor protein were detected during the LPS treatment. Leptin produced a substantial increase in the stability of the LPS-induced KC mRNA, and the synergistic effect of leptin on LPS-induced KC mRNA expression was further augmented by cycloheximide (CHX). Pyrrolidine dithiocarbamate (PDTC) did not block the synergistic effect of leptin on LPS-induced KC mRNA expression in mouse peritoneal macrophages. These data suggest that although leptin has no direct effect on the expression of lymphotactin, RANTES, eotaxin, MIP-1$\beta$, MIP-1$\alpha$, MIP-2, MCP-1, IP-10, TCA-3, and KC mRNA in mouse peritoneal macrophages, the synergistic effect of leptin on the expression of LPS-induced KC mRNA has the possibility that LPS might induce the expression of the Ob-Rb receptor or an unknown gene(s) that sensitizes macrophages to the synergistic function of leptin. Therefore, further studies are necessary to examine leptin as a regulatory factor of chemokine production.

• 대한한방내과학회지
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• 제27권2호
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• pp.521-532
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• 2006

Backgrounds and Objectives: A major goat in asthma therapy isto reduce or prevent the inflammatory response associated with bronchial hyperresponsiveness, reversible airway obstruction and airway remodelling. Many studies have shown that eosinophilic infiltration is a prominent feathure in the pathophysiology of asthma. The importance of the Presence of eosinophils in the airways of asthmatics has long been recognized, but the mechanism by which these cells are recruited and retained in the lung are only now being elucidated Production of chemotactic cytokines by bronchial epithelial cells may contribute to the local accumulation of eosinophils in Patients with bronchial asthma. This study was designed to investigate the inhibitory effect of extraction of herbal dicoction, Gamichungsangbohatang(GMCSBHT) on eosinophil chemotactic cytokines. Material and Methods:We used water and 70% ethanol extracts of GMCSBHT and pulmonary epithelial cell lines A549(human type II -like epithelial cells). We estimated cytotoxic effects of GMCSBHT, and estimated the effects of water and 70% ethanol extracts of GMCSBHT on chemokines from prestimulated A549 cells by sandwich ELISA. Results: Chemokines of eotaxin, IL-8 were inhibited by GMCSBHT in dose-dependent manner. And ethanol extract of GMCSBHT has more inhibitory effects on eotaxin, IL-8 than hot water extract. Conculusions: These findings indicate that the supression of the expression of chemokines can be accomplished by GMCSBHT treatment, so GMCSBHT may inhibit the iuflammatory process by eosinophils in asthma.

• 한국대기환경학회지
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• 제24권3호
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• pp.321-328
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• 2008

The number of patient with allergic asthma and atopy have increased in the cities of Korea steadily. In order to elucidate the primary factor, we investigated whether the house dust particles collected from an apartment of the middle classes has promoting effects of allergen-related airway inflammation and airway hyperresponsiveness. Mice were treated with 0.1 mL of 1 mg/mL of house dust particles suspension by intratracheal instillation once weekly for 10 weeks combined with ovalalbumin (OVA) sensitization. Intratracheal instillation of house dust particles and OVA sensitization caused an increase in the level of serum L-lactate dehydrogenase (LDH), immunoglobulun-E (IgE) and histamine, and an elevation in respiratory resistance. It also enhanced infiltration of eosinophils in the bronchoalveolar lavage fluid (BALF) of mice, IgE and eotaxin expression in blood, and T helper type 2 cell derived cytokine levels such as of interleukin (IL)-4, IL-13 and IL-5 in the BALF. However, it did not influence T helper type 1 cytokine such as interferon-gamma in the BALF. These results indicate that house dust particles elevate allergen-related airway inflammation and airway hyperresponsiveness in mice and may play an important role in the aggravation of asthma and atopy in Korea.

• Environmental Analysis Health and Toxicology
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• 제25권2호
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• pp.121-129
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• 2010

This study was carried out to investigate whether asian yellow sand dust (AS) has promoting effects of allergen-related airway inflammation and airway hyperresponsiveness, because the number of patient with allergic asthma and atopy, and with chronic bronchial inflammation and pneumonia have increased steadily in the cities of Korea. The appearance of AS collected was all round and flat, and the diameter was mostly below about 5 ${\mu}m$. When mice were treated with AS suspension by intratracheal instillation combined with ovalalbumin(OVA) sensitization chronically, the level of serum L-lactate dehydrogenase (LDH), IgE and histamine, and respiratory resistance was increased. Intratracheal instillation of AS and OVA also enhanced infiltration of eosinophils in the bronchoalveolar lavage fluid (BALF), IgE and eotaxin expression, and T helper type 2 cell derived cytokines of interleukin (IL)-4, IL-13 and IL-5 as major contributors to allergy and asthma. These results indicate that AS elevates allergen-related airway inflammation and airway hyperresponsiveness in mice and may play an important role in the aggravation of respiratory diseases in Korea.

• 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.

• Advances in Traditional Medicine
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• 제7권5호
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• pp.518-526
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• 2008

Recently a major goal in asthma therapy is to reduce or prevent the inflammatory response of airway. Eosinophilic accumulation in the tissue is a prominent feature of allergic diseases including asthma. Production of chemokines by bronchial epithelial cells may contribute to the allergic inflammation by recruiting eosinophils. In this study we evaluated the inhibitory effect of Gamichungsangbohatang (GMCSBHT), used traditionally in treating asthma, on secretion of chemokines for eosinophils in human A549 epithelial cells. Chemokines such as eotaxin, RANTES, IL-8 were inhibited in a dose-dependent manner, but IL-16 showed no inhibition by GMCSBHT. These findings indicate that GMCSBHT might be a therapeutic value in treating asthma by suppression of chemokines secretion associated with local accumulation of eosinophils.

• 동의생리병리학회지
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• 제20권3호
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• pp.710-718
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• 2006

The present study was carried out to investigate the effect of Chihyo-san (CHS) administration on asthma induced by Alum/OVA treatment in the mice. In CHS-treated animal group, lung weight, which was increased after asthma induction, was significantly decreased, and total number of cells in the lung, peripheral lymph node (PLN) and spleen tissue was significantly decreased in CHS-treated group compared to the asthma control group. The number of immune cells including natural killer (NK) cells in asthmatic animals was largely regulated by CHS treatment, showing a similar pattern as that of CsA-treated positive control group. Levels of mRNAs encoding inflammatory cytokines IL-5, IL-13, $TNF-{\alpha}$, and eotaxin were determined by RT-PCR in the lung tissue and showed decreases in CHS-treated group to the similar levels of CsA-treated control group, Histamine level in the serum was significantly lower in CHS-treated group than asthma-induced control group. Both haematoxylin and eosin staining and Masson's trichrome staining results showed decreased number of inflammatory cells, reduced immune cell infiltration, and normalized epithelial cell layering in the bronchial tissue of CHS-treated mouse group. Thus, the present findings suggest that CHS may be useful for protecting bronchial tissues from consistent inflammatory damages that occur in asthma patients.