• Journal of Microbiology and Biotechnology
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• 제31권8호
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• pp.1109-1114
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• 2021

Chlamydia pneumoniae is a type of pathogenic gram-negative bacteria that causes various respiratory tract infections including asthma. Chlamydia species infect humans and cause respiratory infection by rupturing the lining of the respiratory which includes the throat, lungs and windpipe. Meanwhile, the function of interleukin-4 (IL-4) in Ch. pneumoniae respiratory infection and its association with the development of airway hyperresponsiveness (AHR) in adulthood and causing allergic airway disease (AAD) are not understood properly. We therefore investigated the role of IL-4 in respiratory infection and allergy caused by early life Chlamydia infection. In this study, Ch. pneumonia strain was propagated and cultured in HEp-2 cells according to standard protocol and infant C57BL/6 mice around 3-4 weeks old were infected to study the role of IL-4 in respiratory infection and allergy caused by early life Chlamydia infection. We observed that IL-4 is linked with Chlamydia respiratory infection and its absence lowers respiratory infection. IL-4R α2 is also responsible for controlling the IL-4 signaling pathway and averts the progression of infection and inflammation. Furthermore, the IL-4 signaling pathway also influences infection-induced AHR and aids in increasing AAD severity. STAT6 also promotes respiratory infection caused by Ch. pneumoniae and further enhanced its downstream process. Our study concluded that IL-4 is a potential target for preventing infection-induced AHR and severe asthma.

• 한국미생물·생명공학회지
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• 제50권2호
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• pp.310-318
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• 2022

The fruits of Paulownia tomentosa (Thunb.) (PT) Steud. have been reported to exert a variety of biological activities. A previous study confirmed that compounds isolated from PT fruits (PTF) exerted anti-inflammatory effects on TNF-α-stimulated airway epithelial cells. However, there is no report on the protective effects of PTF on acute lung injury (ALI). Here, we examined the ameliorative effects of PTF in an experimental animal model of lipopolysaccharide (LPS)-induced ALI. In ALI mice, increased levels of inflammatory cell influx were confirmed in the lungs of mice, and an increase of microphage numbers, TNF-α, IL-6 and MCP-1 production and protein content were detected in mouse bronchoalveolar lavage fluid. However, these increases were significantly reversed with PTF pretreatment. In addition, PTF inhibited the increased expression of iNOS and COX-2 in the lungs of ALI mice. Furthermore, the upregulation of MAPK and NF-κB activation was decreased in the lungs of ALI mice by PTF. In the in vitro experiment, PTF pretreatment exerted an anti-inflammatory effect by inhibiting the secretion of nitric oxide, TNF-α and IL-6 in LPS-stimulated RAW264.7 macrophages. Collectively, these results indicated that PTF has ameliorative effects on airway inflammation in an experimental animal model of ALI.

• 대한한방내과학회지
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• 제45권2호
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• pp.287-302
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• 2024

Background: Bronchiectasis is a chronic respiratory condition leading to recurrent respiratory infections. Despite the use of antibiotics and other standard treatments, managing bronchiectasis remains challenging due to the frequent recurrence of airway infections and concerns about antimicrobial resistance. Given these challenges, traditional Korean medicine (TKM) has gained attention due to its potential to reduce the frequency of respiratory infections, possibly minimizing the need for antibiotics. Case report: A 59-year-old female with bronchiectasis experienced recurrent pneumonia and was treated with antibiotics for over 2 weeks without any significant improvement in clinical symptoms. She received comprehensive Korean medicine treatment, including herbal medicine (Sikyungbanha-tang combined with Bigwabojungikki-tang-gami), acupuncture, and Chuna manual therapy, for pulmonary rehabilitation. Post-treatment, clinically meaningful improvements were observed in symptoms, serum C-reactive protein (CRP) levels, and bronchopneumonic lesions on chest X-rays. Conclusion: This case suggests that complex traditional Korean medicine treatments for recurrent chronic airway inflammation due to bronchiectasis can lead to clinically significant improvements in symptoms and help to prevent recurrence.

• 한방안이비인후피부과학회지
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• 제28권4호
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• pp.74-91
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• 2015

Background and Objective : Asthma is a chronic inflammatory disease at the mucosa and is associated with excess production of Th2 cytokine and eosinophil accumulation in lung.Gamchomahwang-tangextract(GME) is one of the well known prescription used in oriental medicine for treating asthma. This study was designed to compare the anti-asthmatic effect of GME according to the ratio of 2 compounds.Methods : To examine the effects of GME on asthma, mice were sensitized with 100 ㎍ of OVA and 1 ㎎ of aluminum potassium sulfate(Alum; Sigma) intraperitoneally on day 1 and 15. From day 22, mice were challenged on 3 consecutive days with 5% OVA. The anti-asthmatic effects of GME were evaluated by enhanced pause(Penh), bronchoalveolar lavage fluids (BALF), inflammatory cytokine production and genes expression, serum IgE production. and histological change in lung tissue. GMEⅠ consists of ES and GU in the proportion 2:1(300 ㎎/㎏ group), GMEⅡ consist of ES and GU in the proprtion 4:1(300 ㎎/㎏ group).Results : GMEⅠ,Ⅱ generally inhibited lung inflammation, inflammatory cells infiltration and cytokine production and gene expression such as IL-4, IL-5 and IL-13 in BALF and serum IgE level. GMEⅡ significantly reduced the cytokine production and gene expression such as IL-4, IL-5 and IL-13 in BALF and GMEⅠ decreased cytokine production of IL-4, IL-13 in BALF and gene expression of IL-4, IL-5 in Lung. GMEⅡ potently inhibited the development of Penh and also reduced the number of eosinophil during OVA-induced AHR(airway hyper-reactivity). Overall the results show that GMEⅡ has more effect on inhibiting production, gene expression of cytokine, serum IgE level and development of Penh than GMEⅠ. Consequently, GMEⅡ might be more effective than GMEⅠ at inhibiting allergic asthma on the OVA-induced mice model.Conclusion : These results indicate that GME has a deep inhibitory effects on airway inflammation and hyperresponsiveness in mice model of asthma and that suppression of IL-4, IL-5, IL-13 expression and decrease of IL-4, IL-5, IL-13 production in BALF might contribute this effect. Hence, the results indicate that GME might be useful herbal medicine of allergic asthma. As a result, GMEⅡ mght be superior to GMEⅠ in the aspect of anti-asthmatic effect on the OVA-induced mice model.

• 대한한방내과학회지
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• 제41권3호
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• pp.339-349
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• 2020

Objective: This study aimed to evaluate anti-inflammatory and antitussive expectoration effects of Friltillariae Thunbergii Bulbus (FTB) in a mouse model. Materials and Methods: To evaluate the anti-inflammatory effects of the FTB, we conducted in vitro experiments using RAW264.7 cells. An MTT assay and enzyme-linked immunosorbent assay (ELISA) were carried out to examine the anti-inflammatory effects of FTB. The expectorant effect on phenol red secretion, the antitussive effect on cough induced by ammonia solution, and leukocyte increased inhibition effects in acute airway inflammation in the animal model were confirmed. Results: FTB did not show cytotoxicity in the experimental group at 10, 30, 50, 100, 300, or 500 ㎍/ml and significantly inhibited the increase of NO, TNF-α and IL-6 in the experimental groups at 30, 50, 100, 300, and 500 ㎍/ml concentrations. In sputum, cough, and acute airway inflammation animal models, FTB significantly increased phenol red secretion in the 400 mg/kg administration group. FTB significantly reduced the number of coughs and significantly increased cough delay time in both 200 and 400 mg/kg dose groups. FTB decreased the white blood cell count in BALF (bronchoalveolar lavage fluid) in the 400 mg/kg administration group. Conclusion: Our study revealed that FTB elicits antitussive and expectorant effects by inhibiting inflammatory cytokines, increasing sputum secretion, suppressing cough, and reducing inflammatory cells. We concluded that FTB is a highly promising agent for respiratory tract infection with therapeutic opportunities.

• Clinical and Experimental Pediatrics
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• 제49권9호
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• pp.977-982
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• 2006

목 적 : M. pneumoniae는 기도 점막의 상피세포에서 증식하면서 호흡기 질환을 일으키며 기관지 천식의 발생이나 악화와 관계된다고 알려져 있다. IL-6은 급성 염증을 유도하는 사이토카인으로 B 세포의 분화에 관여하며 Th2 염증반응을 촉진시키며, IL-8은 기도에서 염증부위로의 세포이동을 매개하는 케모카인으로 알레르기 염증 반응에 밀접한 관련을 가진다. 기도 상피세포에서 생성되는 NO는 기도 염증과 기도과민성의 조절에 중요하다. VEGF는 천식에서 기도개형에 주된 역할을 담당한다. 본 연구에서는 기관지 상피세포에 M. pneumoniae를 감염시켰을 때 IL-6, IL-8, NO 및 VEGF의 발현을 살펴보았다. 방 법 : M. pneumoniae를 기관지 상피 세포주인 A549 세포에 감염시킨 후 여러 시간 간격으로 배양하여 세포와 배양 상층액을 수거하였다. 면역 형광 염색과 M. pneumoniae 16S ribosomal RNA gene의 oligonucleotide primers를 이용한 중합효소 연쇄반응을 시행하여 감염을 확인하였다. IL-6, IL-8, VEGF 단백질 생성은 ELISA kit를 이용하여 정량하였고, NO는 Griess 반응을 이용하여 측정하였다. 역전사 중합효소 연쇄반응을 이용하여 IL-6, IL-8, VEGF의 mRNA 발현을 관찰하였다. 결 과 : 기관지 상피세포에 M. pneumoniae를 감염시킨 후 시간이 지남에 따라 IL-6, IL-8, NO, VEGF의 생성이 증가하였고, IL-6, IL-8, VEGF mRNA 발현이 증가됨을 관찰하였다. 결 론 : M. pneumoniae 감염은 IL-6, IL-8, NO, VEGF 등의 매개물질의 발현을 증가시켜 기관지 천식의 알레르기 염증반응에 관여할 것으로 사료된다.

• Tuberculosis and Respiratory Diseases
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• 제48권2호
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• pp.223-235
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• 2000

배 경: 액체환기가 손상된 폐에 긍정적인 영향을 주는 한 기전으로 perfluorocarbon(PFC)이 기도상피세포에서 chemokine발현을 억제할 수 있는 지를 관찰하기 위해 본 연구를 시행하였다. 방 법: 기도 상피세포로는 A549 세포주를, PFC로는 perfluorodecalin을, PFC의 노출은 Transwell$^{(R)}$배양접시의 lower chamber를 이용하여 시행하였다. PFC가 말초혈액 탄핵구층(peripheral blood mononuclear cell : PBMC)의 기능을 억제해서 A549세포의 chemokine 발현을 억제할 수 있는지를 관찰하기 위해서 PBMC를 분리하여 Transwell$^{(R)}$ 접시에서 배양하면서 lipopolysaccharide(LPS, 10 ${\mu}g/mL$)로 자극과 PFC의 노출에 따라 군을 나누었으며 24시간 후 그 배양 상층액을 포함한 conditioned media(CM)으로 24시간 동안 A549세포를 자극한 후 chemokine발현을 측정하였다. 또한 PFC가 직접 기도 상피세포의 기능을 억제할 수 있는 지를 관찰하기 위해서 A549 세포를 Transwell$^{(R)}$ 접시에서 배양하면서 interleukin-l$\beta$(IL-1$\beta$, 10 ng/ml), TNF-$\alpha$(10 ng/ml)로 각각 혹은 동시에 24시간동안 자극하면서 PFC노출여부에 따른 IL-8과 RANTES발현 정도를 비교하였다. Chemokine 발현은 IL-8과 RANTES의 단백에 대한 ELISA와 mRNA는 Northern analysis를 통하여 분석하였다. 결 과: 1. LPS로 자극한 PBMC의 배양상층액을 포함한 CM로 A549세포를 자극하였을 때 IL-8과 RNATES mRNA 발현과 면역반응성 단백 생성이 의미 있게 상승하였으나(p<0.05) PFC노출여부에 따른 유의한 차이는 관찰할 수 없었다. 2. TNF-$\alpha$와 IL-1$\beta$ 모두 A549세포에서 IL-8과 RANTES mRNA자발현과 면역반응성 단백 생성의 증가를 가져왔으나(p<0.05) PFC노출에 따른 유의한 차이는 관찰할 수 없었다. 결 론: 기도 상피세포의 chemokine발현 감소를 통한 항염증 작용은 액체환기시 보이는 염증반응 감소에 큰 기여를 하지 않을 것으로 생각되며 추후 액체환기시 관찰되는 염증반응의 감소의 기전에 대한 연구가 더 필요할 것으로 사료된다.

• 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.

• Clinical and Experimental Pediatrics
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• 제56권4호
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• pp.151-158
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• 2013

Purpose: We investigated the mRNA levels of peroxisome proliferator-activated receptor (PPAR)-${\alpha}$, PPAR-${\gamma}$, adipokines, and cytokines in the lung tissue of lean and obese mice with and without ovalbumin (OVA) challenge, and the effect of rosiglitazone, a PPAR-${\gamma}$ agonist. Methods: We developed 6 mice models: OVA-challenged lean mice with and without rosiglitazone; obese mice with and without rosiglitazone; and OVA-challenged obese mice with and without rosiglitazone. We performed real-time polymerase chain reaction for leptin, leptin receptor, adiponectin, vascular endothelial growth factor (VEGF), tumor necrosis factor (TNF)-${\alpha}$, transforming growth factor (TGF)-${\beta}$, PPAR-${\alpha}$ and PPAR-${\gamma}$ from the lung tissue and determined the cell counts and cytokine levels in the bronchoalveolar lavage fluid. Results: Mice with OVA challenge showed airway hyperresponsiveness. The lung mRNA levels of PPAR${\alpha}$ and PPAR-${\gamma}$ increased significantly in obese mice with OVA challenge compared to that in other types of mice and decreased after rosiglitazone administeration. Leptin and leptin receptor expression increased in obese mice with and without OVA challenge and decreased following rosiglitazone treatment. Adiponectin mRNA level increased in lean mice with OVA challenge. Lung VEGF, TNF-${\alpha}$, and TGF-${\beta}$ mRNA levels increased in obese mice with and without OVA challenge compared to that in the control mice. However, rosiglitazone reduced only TGF-${\beta}$ expression in obese mice, and even augmented VEGF expression in all types of mice. Rosiglitazone treatment did not reduce airway responsiveness, but increased neutrophils and macrophages in the bronchoalveolar lavage fluid. Conclusion: PPAR-${\alpha}$ and PPAR-${\gamma}$ expressions were upregulated in the lung tissue of OVA-challenged obese mice however, rosiglitazone treatment did not downregulate airway inflammation in these mice.

• The Korean Journal of Physiology and Pharmacology
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• 제24권4호
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• pp.329-338
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• 2020

Rhinorrhea in allergic rhinitis (AR) is characterized by the secretion of electrolytes in the nasal discharge. The secretion of Cl^- and HCO₃^- is mainly regulated by cystic fibrosis transmembrane conductance regulator (CFTR) or via the calcium-activated Cl^- channel anoctamin-1 (ANO1) in nasal gland serous cells. Interleukin-4 (IL-4), which is crucial in the development of allergic inflammation, increases the expression and activity of ANO1 by stimulating histamine receptors. In this study, we investigated ANO1 as a potential therapeutic target for rhinorrhea in AR using an ANO1 inhibitor derived from a natural herb. Ethanolic extracts (30%) of Spirodela polyrhiza (SP_EtOH) and its five major flavonoids constituents were prepared. To elucidate whether the activity of human ANO1 (hANO1) was modulated by SP_EtOH and its chemical constituents, a patch clamp experiment was performed in hANO1-HEK293T cells. Luteolin, one of the major chemical constituents in SP_EtOH, significantly inhibited hANO1 activity in hANO1-HEK293T cells. Further, SP_EtOH and luteolin specifically inhibited the calcium-activated chloride current, but not CFTR current in human airway epithelial Calu-3 cells. Calu-3 cells were cultured to confluency on transwell inserts in the presence of IL-4 to measure the electrolyte transport by Ussing chamber. Luteolin also significantly inhibited the ATP-induced increase in electrolyte transport, which was increased in IL-4 sensitized Calu-3 cells. Our findings indicate that SP_EtOH and luteolin may be suitable candidates for the prevention and treatment of allergic rhinitis. SP_EtOH^- and luteolin-mediated ANO1 regulation provides a basis for the development of novel approaches for the treatment of allergic rhinitis-induced rhinorrhea.