• IMMUNE NETWORK
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• v.16 no.4
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• pp.201-210
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• 2016

Allergic inflammation requires the orchestration of altered gene expression in the target tissue and in the infiltrating immune cells. The transcription factor STAT6 is critical in activating cytokine gene expression and cytokine signaling both in the immune cells and in target tissue cells including airway epithelia, keratinocytes and esophageal epithelial cells. STAT6 is activated by the cytokines IL-4 and IL-13 to mediate the pathogenesis of allergic disorders such as asthma, atopic dermatitis, food allergy and eosinophilic esophagitis (EoE). In this review, we summarize the role of STAT6 in allergic diseases, its interaction with the co-factor PARP14 and the molecular mechanisms by which STAT6 and PARP14 regulate gene transcription.

• Biomolecules & Therapeutics
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• v.22 no.1
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• pp.62-67
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• 2014

This study was designed to find some potential natural products and/or constituents inhibiting proinflammatory cytokine generation in lung inflammation, since cytokines such as tumor necrosis factor-${\alpha}$ (TNF-${\alpha}$) and interleukin-6 (IL-6) are pivotal for provoking airway inflammation. In our preliminary screening procedure, the 70% ethanol extract of the leaves of Perilla frutescens (PFE) was found to clearly inhibit TNF-${\alpha}$ production in the lung at 100 mg/kg, after intranasal lipopolysaccharide treatment of mice. Based on this result, ten constituents including phenylpropanoids (allyltetramethoxybenzene, caffeic acid, dillapiole, elemicin, myristicin, nothoapiole, rosmarinic acid methyl ester, rosmarinic acid) and monoterpenes (perilla aldehyde and perilla ketone) were successfully isolated from the extract. Among them, elemicin and myristicin were found for the first time to concentration-dependently inhibit IL-$1{\beta}$-treated IL-6 production from lung alveolar epithelial cells (A549) at concentrations of $10-100{\mu}M$. These findings suggest that the phenylpropanoids including elemicin and myristicin have the potential to be new inhibitory agents against lung inflammation and they may contribute, at least in part, to the inhibitory activity of PFE on the lung inflammatory response.

• Microbiology and Biotechnology Letters
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• v.36 no.4
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• pp.343-352
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• 2008

Frankincense, the gum resin derived from Boswellia species, is complex mixtures composed of about $5{\sim}9%$ highly aromatic essential oil, $65{\sim}85%$ alcohol-soluble resins, and the remaining water-soluble gums. The anti-inflammatory properties of frankincense, alcohole-soluble resins, are well-recognized, but the question of whether aromatic essential oil also plays a role in the allergic asthma remains unanswered. This study was performed to evaluate anti-inflammatory effects of Boswellia sacra essential oil (BSEO) on ovalbumin (OVA)-induced asthma mouse model. BALB/c mice after intraperitoneal OVA sensitization were challenged with intratracheal OVA. One experimental group was inhaled with 0.3% BSEO for the later 8 weeks. BALB/c mice were sensitized and challenged with OVA and developed airway eosinophilia, mucus hypersecretion, and airway hyperresponsiveness. In contrast, the BSEO treated mice had reduced a number of eosinophils among BALF cells, goblet cell hyperplasia, and airway hyperresponsiveness. Cytokine analysis of BALF revealed that BSEO caused an increase in Th1 cytokine (interferon-$\gamma$ (IFN-$\gamma$)) and a decrease in Th2 cytokines (interleukin-4 (IL-4), IL-5 and IL-13) levels. In addition, the OVA-specific serum IgE and eotaxin levels were also reduced. In mice inhaled BSEO, $CD4^+$, $CD3^+/CCR3^+$, and $B220^+/CD23^+$ mediastinal lymph nodes cells were also decreased. These results suggest that inhaled BSEO as a immunomodulator in Th1/Th2 mediated asthma may have therapeutic potential for the treatment in allergic airway inflammation by a simple, cost-effective way.

• Journal of Microbiology and Biotechnology
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• v.25 no.5
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• pp.589-597
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• 2015

It has been reported that overexpression of MUC5AC induced by excessive inflammation leads to airway obstruction in respiratory diseases such as chronic obstructive pulmonary disease and asthma. 15-Hydroxyeicosatetraenoic acid (15-HETE) has been reported to have anti-inflammatory effects, but the role of 15-HETE in respiratory inflammation has not been determined. Therefore, the aim of this study was to investigate the effects of 15-HETE on MUC5AC expression and related pathways. In this study, phorbol-12-myristate-13-acetate (PMA) was used to stimulate NCI-H292 bronchial epithelial cells in order to examine the effects of 15-HETE. 15-HETE inhibited PMA-induced expression of MUC5AC mRNA and secretion of MUC5AC protein. Moreover, 15-HETE regulated matrix metallopeptidase 9 (MMP-9), mitogen-activated protein kinase kinase (MEK), and extracellular signal-regulated kinase (ERK). In addition, 15-HETE decreased the nuclear translocation of specificity protein-1 (Sp-1) transcription factor and nuclear factor κB (NF-κB). Furthermore, 15-HETE enhanced the transcriptional activity of peroxisome proliferator-activated receptor gamma (PPARγ) as a PPARγ agonist. This activity reduced the phosphorylation of protein kinase B (PΚB/Akt) by increasing the expression of phosphatase and tensin homolog (PTEN). In conclusion, 15-HETE regulated MUC5AC expression via modulating MMP-9, MEK/ERK/Sp-1, and PPARγ/PTEN/Akt signaling pathways in PMA-treated respiratory epithelial cells.

• The Korean Journal of Physiology and Pharmacology
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• v.22 no.5
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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.

• Tuberculosis and Respiratory Diseases
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• v.50 no.2
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• pp.196-204
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• 2001

Background : Bronchial asthma is characterized by a reversible airway obstruction, airway hyperresponsiveness, and eosinophilic airway inflammation. The bronchodilator response(BDR) after short acting beta agonist inhalation and PC20 with methacholine inhalation are frequently used for diagnosing bronchial asthma. However, the relationship between the presence of a bronchodilator response and the degree of airway hyperresponsiveness is uncertain. Therefore, the availability of a eosinophil cationic protein (ECP) and a correlation ECP with a bronchodilator response and airway hyperresponsiveness was investigated. Method : A total 71 patients with a moderate to severe degree of bronchial asthma were enrolled and divided into two groups. 31 patients with a positive bronchodilator response and 38 patients with a negative bronchodilator response were evaluated. In both groups, the serum ECP, peripheral blood eosinophil counts, and total IgE level were measured and the methacholine bronchial provocation test was examined. Results : There were no differences observed in age, sex, atopy, and baseline spirometry in both groups. The peripheral eosinophil counts showed no difference in both groups, but the ECP level in group 1 (bronchodilator responder group) was higher than in group 2(non-bronchodilator responder group) ($22.4{\pm}20.7$ vs $14.2{\pm}10.4$, mean$\pm$SD). The PC20 in group 1 was significantly lower than in group 2 ($1.14{\pm}1.68$ vs $66{\pm}2.98$). There was a significant positive correlation between the BDR and ECP, and a negative correlation between the bronchial hyperresponsiveness and ECP. Conclusion : The bronchodilator response significantly correlated with the bronchial hyperresponsiveness and serum ECP in the moderate to severe asthma patients. Hence, the positive bronchodilator response is probably related with active bronchial inflammation and may be used as a valuable index in treatment, course and prognosis of bronchial asthma.

• Tuberculosis and Respiratory Diseases
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• v.48 no.6
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• pp.922-931
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• 2000

Background : It has been well known that bronchia1 asthma is a chronic airway inflammatory disorder. Recently, sputum induced with hypertonic saline was introduced as a simple and useful nonivasive medium to investigate airway inflammation and symptom severity in patients with asthma. We examined the eosinophil, eosinophil cationic protein (ECP), interleukin(IL)-3, IL-5, granulocyte-macrophage colony-stimulating facta (GM-CSF), and nitric oxide (NO) derivatives in induced sputum from patients with bronchia1 asthma in order to determine the role of NO and various inflammatory cytokines as a useful markers of airway inflammation or changes in pulmonary function tests and symptoms. Methods : A total 30 patients with bronchia1 asthma received oral prednisolone 30 mg daily for 2 weeks. Forced expiratory volume in one second ($FEV_1$), total blood eosinophil count and induced sputum eosinophil count, ECP, IL-3, IL-5, GM-CSF, and NO derivatives were determined before and after the administration of prednisolone. Results : Of the 30 patients, 13 (43.3%) were male and 17 (56.7%) were female. The mean age of patients was 41.8 years (range 19-64 years). Two patients could not produce sputum at the second study and 3 could not be followed up after their first visit. Two weeks after the prednisolone administration, there was a significant increase in $FEV_1$ (% of predicted value) from 78.1$\pm$20.6 % to 90.3$\pm$ 18.3 % (P<0.001). The eosinophil percentages in induced sputum were significantly decreased after treatment with prednisolone, with values of 56.1$\pm$27.2 % versus 29.6$\pm$21.3 % (P<0.001), and ECP were $134.5\pm68.1\;{\mu}g/L$ versus $41.5\pm42.4\;{\mu}g/L$ (P<0.001) respectively. After the prednisolone treatments, the eotaxin concentration also showed a decreasing tendency from 26.7$\pm$12.8 pg/ml to 21.7$\pm$8.7 pg/ml. There was a decreasing tendency but no significant differences in total blood eosinophil count (425.7$\pm$265.9 vs 287.7$\pm$294.7) and in the concentration of NO derivatives ($70.4\pm44.6{\mu}mol/L$ vs $91.5\pm48.3\;{\mu}mol/L$) after the prednisolone treatments. IL-3, IL-5, GM-CSF were undetectable in the sputum of most subjects either before the prednisolone treatments or after the treatments. Before the prednisolone treatments, a significant inverse correlation was observed between FEV1 and sputum ECP (r=-D.364, P<0.05) and there was a significant correlation between sputum eosinophils and eotaxin (r=0.369, P<0.05) Conclusion : The eotaxin and ECP concentration in induced sputum may be used as markers of airway inflammation after treatments in bronchia1 asthma. In addition, the measurement of sputum eosinophil percent ages is believed to be a simple method displaying the degree of airway inflammation and airway obstruction before and after the prednisolone treatment in bronchia1 asthma. However, unlike exhaled NO, the examination of NO derivatives with Griess reaction in induced sputum is considered an ineffective marker of changing airway inflammation and obstructing symptoms.

• Journal of Haehwa Medicine
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• v.18 no.1
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• pp.1-8
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• 2009

This study analyzed the contents of the research papers of Complementary Medicine concerning the inhalation drug for asthma published in Pubmed during lately 10 years. As a result, the following conclusion was drawn. 1. There were 5 papers concerning 2 review articles, 2 experimental studies and 1 clinical study. 2. Interventions of research papers are glutathione, microorganism fermentation extract (EM-X), ginkgolide and compound Chinese herbal monomer recipe (ligustrazin, baicalin, ginkgolide). 3. There is no controlled study for effect of inhaled glutathione, on the contrary it induced bronchial constriction in sulfites sensitive asthmatics. 4. Inhalation of EM-X reduced airway hyper-reactivity and level of IL-4, IL-5 and IL-13 in OVA challenged asthmatic mice. 5. Ginkgolide nebulized inhalation reduced symptomatic scorings and eosinophil cationic protein, improved FEV1 and PEF. 6. Compound Chinese herbal monomer (CHM) recipe reduced blood eosinophil count, eosinophil count and total cell cound in BALF, depressed airway hyper-responsiveness and airway inflammation.

• Journal of the Korean Society of Laryngology, Phoniatrics and Logopedics
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• v.30 no.2
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• pp.128-131
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• 2019

Acute supraglottitis is characterized by an inflammation and edema of the supraglottic region and a potential life-threatening condition because of its risk for sudden upper airway compromise. Prompt diagnosis, administration of broad spectrum antibiotics, and airway management is pivotal for reducing serious complications. In the immunocompromised host, microorganisms are more likely to elicit mucosal inflammations, thus clinicians should pay attention to those patients for prompt removal of the causes of immune disruption. Here we report a case of acute adult supraglottitis with neutropenia caused by anti-thyroid drug with a review of the related literatures.

• Korean Journal of Bronchoesophagology
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• v.4 no.1
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• pp.117-121
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• 1998

Relapsing polychondritis is a rare disesase involving any cartilaginous structure of entire body and is characterized by recurrent episode of inflammation and degeneration of cartilage and most commonly involve ear, nose, larynx, trachea, ribs, Eustachian tube, etc. Its signs and symptoms are recurrent swelling of auricle, saddle nose deformity, polyarthralgia, hoarseness and dyspnea, audiovestibular disturbance and cardiovascular abnormality, etc. Characteristic histologic findings are loss of normal basophilic staining of cartilage, perichondrial inflammatory infiltration with plamsa cells, lymphocytes and neutrophils, and finality, destruction of cartilage and replacement with scar tissue. Our case had saddle nose deformity, arthralgia, tracheal collapse, hearig loss and positive histologic finding but no auricular perichnodritis. Her major problem was airway. obstruction due to tracheal collapse. This case was diagnosed with relapsing polychondritis according to the Damiani's criteria. This case indicates that any patients complaining of airway obstruction have to be examined systemically.