• The Korean Journal of Physiology and Pharmacology
• /
• v.25 no.6
• /
• pp.555-564
• /
• 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.

• Molecules and Cells
• /
• v.45 no.11
• /
• pp.833-845
• /
• 2022

Although asthma is a common chronic airway disease that responds well to anti-inflammatory agents, some patients with asthma are unresponsive to conventional treatment. Mesenchymal stem cells (MSCs) have therapeutic potential for the treatment of inflammatory diseases owing to their immunomodulatory properties. However, the target cells of MSCs are not yet clearly known. This study aimed to determine the effect of human umbilical cord-derived MSCs (hUC-MSCs) on asthmatic lungs by modulating innate immune cells and effector T cells using a murine asthmatic model. Intravenously administered hUC-MSCs reduced airway resistance, mucus production, and inflammation in the murine asthma model. hUC-MSCs attenuated not only T helper (Th) 2 cells and Th17 cells but also augmented regulatory T cells (Tregs). As for innate lymphoid cells (ILC), hUC-MSCs effectively suppressed ILC2s by downregulating master regulators of ILC2s, such as Gata3 and Tcf7. Finally, regarding lung macrophages, hUC-MSCs reduced the total number of macrophages, particularly the proportion of the enhanced monocyte-derived macrophage population. In a closer examination of monocyte-derived macrophages, hUC-MSCs reduced the M2a and M2c populations. In conclusion, hUC-MSCs can be considered as a potential anti-asthmatic treatment given their therapeutic effect on the asthmatic airway inflammation in a murine asthma model by modulating innate immune cells, such as ILC2s, M2a, and M2c macrophages, as well as affecting Tregs and effector T cells.

• IMMUNE NETWORK
• /
• v.21 no.3
• /
• pp.19.1-19.18
• /
• 2021

Clinical and molecular phenotypes of asthma are complex. The main phenotypes of adult asthma are characterized by eosinophil and/or neutrophil cell dominant airway inflammation that represent distinct clinical features. Upper and lower airways constitute a unique system and their interaction shows functional complementarity. Although human upper airway contains various indigenous commensals and opportunistic pathogenic microbiome, imbalance of this interactions lead to pathogen overgrowth and increased inflammation and airway remodeling. Competition for epithelial cell attachment, different susceptibilities to host defense molecules and antimicrobial peptides, and the production of proinflammatory cytokine and pattern recognition receptors possibly determine the pattern of this inflammation. Exposure to environmental factors, including infection, air pollution, smoking is commonly associated with asthma comorbidity, severity, exacerbation and resistance to anti-microbial and steroid treatment, and these effects may also be modulated by host and microbial genetics. Administration of probiotic, antibiotic and corticosteroid treatment for asthma may modify the composition of resident microbiota and clinical features. This review summarizes the effect of some environmental factors on the upper respiratory microbiome, the interaction between host-microbiome, and potential impact of asthma treatment on the composition of the upper airway microbiome.

• IMMUNE NETWORK
• /
• v.22 no.5
• /
• pp.40.1-40.24
• /
• 2022

Mesenchymal stem cells (MSCs) are attractive alternatives to conventional anti-asthmatic drugs for severe asthma. Mechanisms underlying the anti-asthmatic effects of MSCs have not yet been elucidated. This study evaluated the anti-asthmatic effects of intravenously administered MSCs, focusing on macrophages and monocytes. Seven-week-old transgenic (Tg) mice with lung-specific overexpression of IL-13 were used to simulate chronic asthma. MSCs were intravenously administered four days before sampling. We examined changes in immune cell subpopulations, gene expression, and histological phenotypes. IL-13 Tg mice exhibited diverse features of chronic asthma, including severe type 2 inflammation, airway fibrosis, and mucus metaplasia. Intravenous administration of MSCs attenuated these asthmatic features just four days after a single treatment. MSC treatment significantly reduced SiglecF^-CD11c^-CD11b⁺ monocyte-derived macrophages (MoMs) and inhibited the polarization of MoMs into M2 macrophages, especially M2a and M2c. Furthermore, MSCs downregulated the excessive accumulation of Ly6c^- monocytes in the lungs. While an intravenous adoptive transfer of Ly6c^- monocytes promoted the infiltration of MoM and Th2 inflammation, that of MSC-exposed Ly6c^- monocytes did not. Ex vivo Ly6c^- MoMs upregulated M2-related genes, which were reduced by MSC treatment. Molecules secreted by Ly6c^- MoMs from IL-13 Tg mice lungs upregulated the expression of fibrosis-related genes in fibroblasts, which were also suppressed by MSC treatment. In conclusion, intravenously administered MSCs attenuate asthma phenotypes of chronic asthma by modulating macrophages. Identifying M2 macrophage subtypes revealed that exposure to MSCs transforms the phenotype and function of macrophages. We suggest that Ly6c^- monocytes could be a therapeutic target for asthma management.

• Journal of Digital Convergence
• /
• v.15 no.6
• /
• pp.297-304
• /
• 2017

The purpose of this study was to investigate the association between antioxidant food intake pattern and asthma control status in Korean adolescents. This study was conducted using data from 1,578 patients diagnosed with asthma among the participants in the 11th online health behavior survey. Statistical analyses were performed for sociodemographic variables, known risk factors for asthma worsening, and all variables which were related to food intake pattern. For final decision, logistic regression analysis was used to estimate the associations between antioxidant food intake and asthma worsening. Male gender and smoking experiences were associated with asthma exacerbation. Low intake of antioxidant foods status also significantly increased asthma exacerbations. Antioxidant food intake and smoking prevention education is important for adolescent asthma patients. It is highly needed to recommend taking fruits and vegetables properly.

• The Journal of Korean Medicine Ophthalmology and Otolaryngology and Dermatology
• /
• v.24 no.1
• /
• pp.36-44
• /
• 2011

Objective : Propolis (PP) has been used in oriental medicine. PP has various biological activities. However, its immunoregulatory and anti-inflammatory activities have not been well studied. In this study, I investigated these activities of PP by using ovalbumin-induced allergic asthma in mice. Methods : To examine the effect of PP on allergic asthma, mice were sensitized with $100{\mu}g$ of OVA and 1mg of aluminum potasssium sulfate (Alum; Sigma) intraperitoneally on day 0 and 7. On day 14, mice were challenged on consecutive 3 days with 5% OVA and AHR was assessed 24 hours after the last challenge. To examine severity of AHR, I examined the population of eosinophiles and T cells in spleen and lung and cytokine production in T cells. Futhermore, I examined histological changes during the OVA-induced allergic asthma. Results and Conclusion : PP reduced the population of eosinophil and CD4+ T cells on the OVA-induced AHR mice model. PP also inhibited IL-4 production but increased INF-g production in T cells. These results suggest that PP may be beneficial material for allergic asthma.

• Journal of Physiology & Pathology in Korean Medicine
• /
• v.20 no.3
• /
• pp.710-718
• /
• 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.

• The Korea Journal of Herbology
• /
• v.26 no.4
• /
• pp.49-57
• /
• 2011

Objective : Allergic asthma is a chronic airway disease that affects millions of people in the developed world. The disease is characterized by concurring airway inflammation, Th2 cytokine production, increased mucus secretion, airway hyperresponsiveness (AHR) to inhaled antigen, and pulmonary fibrosis. To investigate the therapeutic and anti-asthmatic effects of Drynariae Rhizoma (DR), we examined the influence of DR on the development of pulmonary eosinophilic inflammation and airway hyperresponsiveness in a mouse model of allergic asthma. Methods : In this study, BALB/c mice were systemically sensitized to ovalbumin (OVA) followed intratracheally, intraperitoneally, and by aerosol allergen challenges. We investigated the effect of DR on airway hyperresponsiveness, pulmonary eosinophilic infiltration, various immune cell phenotypes, Th2 cytokine production and OVA specific IgE production in a mouse model of asthma. Results : In asthmatic mice, we found that DR.treated groups had suppressed eosinophil infiltration, allergic airway inflammation and AHR by suppressing the production of IL-5, IL-13 and OVA specific IgE. Conclusions : Our data suggest that the therapeutic mechanism by which DR effectively treats asthma is based on reductions of Th2 cytokines (IL-5), eotaxin, OVA-specific IgE production and eosinophil infiltration.

• Journal of Physiology & Pathology in Korean Medicine
• /
• v.20 no.4
• /
• pp.973-979
• /
• 2006

Cordyceps sinensis has been clinically used for the treatment of recovering fatigue, promoting the production of body fluid and qi, resolving sputum and arresting cough. Recent studies showed that Cordyceps sinensis produced immune-modulatory, anticarcinogenic and antioxidative effects. But, there are lack of studies regarding the effects of Cordyceps sinensis on the asthma. So, this study was performed to investigate the oral administrated effects of this herb against the disease. Asthma was induced to Balb/c mouse by i.p. injection and aerosol immunization with ovalbumin, and the change of the eosinophil number in the bronchoalveolar avage fluid(BALF) was observed. Concentrations of Interleukine-4(IL-4), Interleukine-5(IL-5) in BALF and splenocyte were assessed by ELISA, ImmunoglobinG(IgG) and ImmunoglobinE(IgE) from serum were calculated by same method. We found that the effects of Cordyceps sinensis in asthma mouse was implicated in reductions of IL-4, IL-S released from type2 T helper (Th2) cell, and decreases of IgE from plasma cell. These findings suggest that Cordyceps sinensis can produce anti-asthmatic effect, which may play a role in allergen-induced asthma therapy.

• YAKHAK HOEJI
• /
• v.47 no.4
• /
• pp.244-251
• /
• 2003

Asthma is a chronic inflammatory disease of the airway and the prevalence rate is increasing. As the burden of asthma to the society is significant due to the increasing hospital admissions and emergency visits, National Heart, Lung and Blood Institute (NHLBI, USA) and World Health Organization (WHO) have developed comprehensive guidelines to help clinicians and patients make appropriate decisions about asthma care. The aim of study was to analyze the pattern of asthma prescriptions based on the national asthma guidelines for the patients visiting primary health care providers. Prescription data for asthma were obtained from the Korean National Health Insurance claims database of January 2002. Ten percent of the primary health care providers were sampled based on their specialty areas, and 20％ of the claim cases were randomly chosen. Study results showed that prescription rate for oral beta-2 agonists was 44.3％, and that for oral theophylline was 46.9％. Oral steroids were prescribed for the 28.2％ of the claims. Utilization of inhalers was low for both bronchodilators (20.3％, beta-2 agonists inhalers), and steroids (8.4％ steroids inhalers). Bronchodilators were more preferred to the longterm anti-inflammatory controllers among the primary health care providers. Prescription rate for antibiotics was 46.0％ for asthmatic patients. Also gastrointestinal drugs were prescribed for 59.0％, antitussives 65.3％, antihistamines 25.3％ and analgesics 29.4％, respectively. This study presented that the prescribing pattern of the primary health care providers for the asthma was quite different from the national and international guidelines. More efforts need to be made to reduce the gap between the present pattern of asthma prescription and the guidelines.