• Allergy, Asthma & Immunology Research
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• 제10권6호
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• pp.614-627
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• 2018

Purpose: Asthma is a heterogeneous disease that responds to medications to varying degrees. Cluster analyses have identified several phenotypes and variables related to fixed airway obstruction; however, few longitudinal studies of lung function have been performed on adult asthmatics. We investigated clinical, demographic, and inflammatory factors related to persistent airflow limitation based on lung function trajectories over 1 year. Methods: Serial post-bronchodilator forced expiratory volume (FEV) 1% values were obtained from 1,679 asthmatics who were followed up every 3 months for 1 year. First, a hierarchical cluster analysis was performed using Ward's method to generate a dendrogram for the optimum number of clusters using the complete post-FEV1 sets from 448 subjects. Then, a trajectory cluster analysis of serial post-FEV1 sets was performed using the k-means clustering for the longitudinal data trajectory method. Next, trajectory clustering for the serial post-FEV1 sets of a total of 1,679 asthmatics was performed after imputation of missing post-FEV1 values using regression methods. Results: Trajectories 1 and 2 were associated with normal lung function during the study period, and trajectory 3 was associated with a reversal to normal of the moderately decreased baseline FEV1 within 3 months. Trajectories 4 and 5 were associated with severe asthma with a marked reduction in baseline FEV1. However, the FEV1 associated with trajectory 4 was increased at 3 months, whereas the FEV1 associated with trajectory 5 was persistently disturbed over 1 year. Compared with trajectory 4, trajectory 5 was associated with older asthmatics with less atopy, a lower immunoglobulin E (IgE) level, sputum neutrophilia and higher dosages of oral steroids. In contrast, trajectory 4 was associated with higher sputum and blood eosinophil counts and more frequent exacerbations. Conclusions: Trajectory clustering analysis of FEV1 identified 5 distinct types, representing well-preserved to severely decreased FEV1. Persistent airflow obstruction may be related to non-atopy, a low IgE level, and older age accompanied by neutrophilic inflammation and low baseline FEV1 levels.

• BMB Reports
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• 제38권1호
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• pp.77-81
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• 2005

The monocyte chemotactic protein-3 (MCP3), on chromosome 17q11.2-q12, is a secreted chemokine, which attracts macrophages during inflammation and metastasis. In an effort to discover additional polymorphism(s) in genes whose variant(s) have been implicated in asthma, we scrutinized the genetic polymorphisms in MCP3 to evaluate it as a potential candidate gene for asthma host genetic study. By direct DNA sequencing in twenty-four individuals, we identified four sequence variants within the 3 kb full genome including 1,000bp promoter region of MCP3; one in promoter region (-420T>C), three in intron (+136C>G, +563C>T, +984G>A) respectively. The frequencies of those four SNPs were 0.020 (-420T>C), 0.038 (+136C>G), 0.080 (+563C>T), 0.035 (+984G>A), respectively, in Korean population (n = 598). Haplotypes, their frequencies and linkage disequilibrium coefficients (|D'|) between SNP pairs were estimated. The associations with the risk of asthma, skin-test reactivity and total serum IgE levels were analyzed. Using statistical analyses for association of MCP3 polymorphisms with asthma development and asthma-related phenotypes, no significant signals were detected. In conclusion, we identified four genetic polymorphisms in the important MCP3 gene, but no significant associations of MCP3 variants with asthma phenotypes were detected. MCP3 variation/haplotype information identified in this study will provide valuable information for future association studies of other allergic diseases.

• 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.

• 생명과학회지
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• 제18권10호
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• pp.1336-1341
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• 2008

기관지를 통하여 발병하는 염증은 대표적인 면역질환의 현상인데 천식이나 아토피 피부염 등에 나타난다. 신선초의 물 추출물이 항천식 활성을 나타내는지를 알아보기 위하여 ovalbumin으로 유도시킨 동물모델을 사용하였다. 마우스에 경구투여하여 폐의 조직을 Haematoxylin-Eosin 염색과 면역조직화학을 이용하여 인터루킨-4 및-13의 발현을 측정한 결과, 신선초의 물 추출물은 $CD4^+$ 세포의 수 및, 인터루킨-4 및 -13의 발현을 억제하는 것으로 나타났다. 이의 결과는 신선초의 물 추출물이 ovalbumin 으로 유도시킨 마우스의 천식 증상을 경감시키는 것으로 이의 활용이 기대된다.

• 한국해양바이오학회지
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• 제12권1호
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• pp.1-10
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• 2020

Asthma is a complex inflammatory disease of the lung characterized by variable airflow obstruction, airway hyperresponsiveness, airway inflammation, and reduction of respiratory function. Its prevalence and incidence are increasing because of the effect of various environmental and lifestyle risk factors. Steroid inhalation, long-acting agonists, and other synthetic drugs are used for the treatment of this disease. However, they have some side effects and show unsatisfied result and response after treatment. Therefore, many researchers have focused on the development of natural product-related treatment for asthma to suppress the side effects and unsatisfied results. Seaweeds contain various bioactive compounds with anti-inflammatory, antibacterial, and anti-oxidant activities. Thus, we investigated the asthma treatment-related literature using marine algae via the Google scholar search engine. Consequently, the literature is rarely investigated, but is increasing steadily. The literature was performed as a comparison study with an ovalbumin-induced group or drug-treated group, and investigated the antiasthma activity of algae ethanol extract. Although many researchers have studied marine algae-derived therapeutic agents for asthma, the amount of literature is rare compared with those of herbal medicine-derived therapeutic agents. Conclusively, we suggest that many researchers should investigate and develop algae-derived therapeutic agents for asthma treatment.

• The Korean Journal of Physiology and Pharmacology
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• 제22권5호
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• pp.481-491
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• 2018

Allergic asthma is one of the most enduring diseases of the airway. The T-helper cells and regulatory T-cells are critically involved in inflammatory responses, mucus hypersecretion, airway remodelling and in airway hyper-responsiveness. Cigarette smoke (CS) has been found to aggravate inflammatory responses in asthma. Though currently employed drugs are effective, associated side effects demand identification and development of novel drugs with negligible or no adverse effects. Rutin, plant-derived flavonoid has been found to possess antioxidant and anti-inflammatory effects. We investigated the ability of rutin to modulate T-cells and inhibit inflammation in experimentally-induced asthma in cigarette smoke exposed mice. Separate groups of neonatal mice were exposed to CS for 10 days from post-natal days 2 to 11. After 2 weeks, the mice were sensitized and challenged with ovalbumin (OVA). Treatment group were given rutin (37.5 or 75 mg/kg body weight) during OVA sensitization and challenge. Rutin treatment was found to significantly inhibit cellular infiltration in the airways and Th2 and Th17 cytokine levels as well. Flow cytometry revealed effectively raised $CD4^+CD25^+Fox3^+$ Treg cells and supressed Th17 cell population on rutin treatment. Airway hyper-responsiveness observed following CS and OVA challenge were inhibited by rutin. $NF-{\kappa}B$ and iNOS, chief regulators of inflammatory responses robustly activated by CS and OVA were down-regulated by rutin. Rutin also inhibited the expression of matrix metalloproteinase 9, thereby aiding in prevention of airway remodelling in asthma thereby revealing to be a potent candidate in asthma therapy.

• Genomics & Informatics
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• 제3권4호
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• pp.149-153
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• 2005

Asthma is an inflammatory airways disease characterized by bronchial hyperresponsiveness and airways obstruction, which results from a complex interaction of genetic and environmental factors. Interleukin (IL)-13 and IL-4 are important in IgE synthesis and allergic inflammation, therefore genes encoding IL-13 and IL-4 are candidates for predisposition to asthma. In the present study, we screened single-nucleotide polymorphisms (SNPs) in IL-13 and IL-4 and examined whether they are risk factors for asthma. We resequenced all exons and the promoter region in 12 asthma patients and 12 normal controls, and identified 18 SNPs including 2 novel SNPs. The linkage disequilibrium(LD) pattern was evaluated with 16 common SNPs, and haplotypes were also estimated within the block. Although IL-13 and IL-4 are localized within 27 kb on chromosome 5q31 and share many biological profiles, this region was partitioned into 2 blocks. One SNP and three SNPs were determined as haplotype-taggingSNPs (htSNPs) within IL-13 and IL-4 haplotype-block, respectively. No significant associations were observed between any of the SNPs or haplotypes and development of asthma in small number of Korean subjects. However, the genetic variants of IL-13 and IL-4 would provide valuable strategies for the genotyping studies in large population.

• Genomics & Informatics
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• 제9권1호
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• pp.12-18
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• 2011

Asthma is a chronic disease associated with airway constriction due to inflammation caused by eosinophils, mast cells, and T lymphocytes, leading to serious chronic illness in children. The eotaxin gene family has been shown to play an important role in the pathogenesis of asthma. We hypothesized that the distinctive variations among the four seasons in Korea may affect the expression of eotaxin polymorphisms, especially in children. We examined the possible effects of birth season (spring, March-May; summer, June-August; fall, September-November; and winter, December-February) on the phenotype of asthma in children. All SNP data sets of the eotaxin-2 and eotaxin-3 genes were collected from 78 asthma patients and 101 controls. Here, we investigated the effects of birth season on the expression of eotaxin-2 and eotaxin-3 in Korean children. Using the HAPLOTYPE procedure with the HTR method in SAS/Genetics, we showed that children born in spring and summer show significant haplotypes in both the eotaxin-2 and eotaxin-3 genes. Thus, the expression of polymorphisms in eotaxin-2 and eotaxin-3 may vary by season.

• 대한본초학회지
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• 제21권1호
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• pp.51-56
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• 2006

Objectives : To clarify the effects of Actinidia polygama and CsA on OVA-induced asthma model, we examined the influence of Actinidia polygama fructus extract (APF) and CsA on the number of regulatory T cells, NKT cells and ${\gamma}{\delta}$ T cells in murine model of asthma. Methods : All mice were immunized on two different days (21 days and 7 days before inhalational exposure) by i.p. injections of OVA in PBS. Seven days after the second sensitization, mice were exposed to aerosolized ovalbumin for 30 min/day on 3 days/week for 12 weeks and APF (400, 40 mg/kg) were orally administered 3 times a week for 8 weeks. Results : The suppressive effects of APF on asthma model were demonstrated by the increase the number of regulatory T cells, ${\gamma}{\delta}$ T cells and by reducing the number of NK T cells. Conclusion : These results indicate that APF has a deep inhibitory effect on airway inflammation and hyperresponsiveness in murine model of asthma by increase the number of regulatory T cells, and ${\gamma}{\delta}$ T cells and by reducing the number of NK T cells.

• The Korean Journal of Physiology and Pharmacology
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• 제25권6호
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• pp.555-564
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• 2021

We investigated the effects of naringenin and morin on IL-5 and ROS production in PMA+ionomycin-treated EL-4 cells with the corroboration of their antioxidant and anti-inflammatory properties using an asthma-induced mouse model. The EL-4 cell line was used to study the outcomes of naringenin or morin, followed by cell viability studies. Western blot analysis and ELISA test were used to determine Th2 mediated cytokines. In vivo studies were carried out on BALB/c mice to induce allergic asthma using ovalbumin administered intraperitoneally. Intracellular ROS was determined using 2',7'-dichlorodihydrofluorescein diacetate, followed by serum enzymatic (AST and ALT) estimations and inflammatory cell count in the bronchoalveolar lavage fluid (BALF) and lung tissues. Histopathological studies were conducted to examine lung tissue-stained architecture. Our findings suggested that naringenin and morin significantly suppressed IL-5 and ROS production via various pathways. Interestingly, by reducing NFAT activity, naringenin and morin stimulated HO-1 expression, thereby suppressing IL-5 secretion due to regulating the transcription factor Nrf2 via P13/Akt or ERK/JNK signalling pathways in EL-4 cells, demonstrating the involvement of HO-1 expression in inhibiting asthmatic inflammation. The increased inflammatory cells in the BALF were substantially decreased by both naringenin and morin, followed by inhibition in the elevated Th-2 cytokines levels. The TNF-α protein levels in an allergic asthma mouse model were significantly reduced by suppressing Akt phosphorylation and eosinophil formation. Recent findings confirmed that naringenin and morin possess the potential to control asthma-related immune responses through antioxidant and anti-inflammatory properties, indicating potential therapeutic agents or functional foods.