• Molecules and Cells
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• v.45 no.6
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• pp.353-361
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• 2022

Chronic rhinosinusitis (CRS) is a multifactorial, heterogeneous disease characterized by persistent inflammation of the sinonasal mucosa and tissue remodeling, which can include basal/progenitor cell hyperplasia, goblet cell hyperplasia, squamous cell metaplasia, loss or dysfunction of ciliated cells, and increased matrix deposition. Repeated injuries can stimulate airway epithelial cells to produce inflammatory mediators that activate epithelial cells, immune cells, or the epithelial-mesenchymal trophic unit. This persistent inflammation can consequently induce aberrant tissue remodeling. However, the molecular mechanisms driving disease within the different molecular CRS subtypes remain inadequately characterized. Numerous secreted and cell surface proteins relevant to airway inflammation and remodeling are initially synthesized as inactive precursor proteins, including growth/differentiation factors and their associated receptors, enzymes, adhesion molecules, neuropeptides, and peptide hormones. Therefore, these precursor proteins require post-translational cleavage by proprotein convertases (PCs) to become fully functional. In this review, we summarize the roles of PCs in CRS-associated tissue remodeling and discuss the therapeutic potential of targeting PCs for CRS treatment.

• BMB Reports
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• v.52 no.4
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• pp.283-288
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• 2019

$Foxp3^+$ regulatory $CD4^+$ T (Treg) cells play an essential role in preventing overt immune responses against self and innocuous foreign antigens. Selective expansion of endogenous Treg cells in response to the administration of interleukin (IL)-2/antibody complex, such as the IL-2/JES6-1 complex (IL-2C) in mice, is considered an attractive therapeutic approach to various immune disorders. Here, we investigated the therapeutic potential of IL-2C in allergic airway inflammation models. IL-2C treatment ameliorated Th17-mediated airway inflammation; however, unexpectedly, IL-2C treatment exacerbated Th2-mediated allergic airway inflammation by inducing the selective expansion of Th2 cells and type-2 innate lymphoid cells. We also found that IL-2 signaling is required for the expansion of Th2 cells in lymphoproliferative disease caused by Treg cell depletion. Our data suggest that IL-2C is selectively applicable to the treatment of allergic airway diseases depending on the characteristics of airway inflammation.

• IMMUNE NETWORK
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• v.11 no.3
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• pp.169-174
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• 2011

Background: NADPH oxidase (NOX) modulates cell proliferation, differentiation and immune response through generation of reactive oxygen species. Particularly, NOX2 is recently reported to be important for regulating Treg cell differentiation of CD4+ T cells. Methods: We employed ovalbumin-induced airway inflammation in wild-type and NOX2-deficient mice and analyzed tissue histopathology and cytokine profiles. Results: We investigated whether NOX2-deficiency affects T cell-mediated airway inflammation. Ovalbumin injection which activates T cell-mediated allergic response increased airway inflammation in wild-type mice, as evidenced by increased immune cell infiltration, allergic cytokine expression, and goblet cell hyperplasia in the lung. Interestingly, NOX2 knockout (KO) mice were more susceptible to allergen-induced lung inflammation compared to wild-type mice. Immune cells including neutrophils, lymphocytes, macrophages, and eosinophils were drastically infiltrated into the lung of NOX2 KO mice and mucus secretion was substantially increased in deficiency of NOX2. Furthermore, inflammatory allergic cytokines and eotaxin were significantly elevated in NOX2 KO mice, in accordance with enhanced generation of inflammatory cytokines interleukin-17 and interferon-${\gamma}$ by CD4+ T cells. Conclusion: These results indicate that NOX2 deficiency favorably produces inflammatory cytokines by T cells and thus increases the susceptibility to severe airway inflammation.

• Korean Journal of Medicinal Crop Science
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• v.17 no.2
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• pp.90-96
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• 2009

The objective of this study was to investigate the effect of crude ginseng total saponins (CGS) against airway inflammation (AI) and airway hyperresponsiveness (AH) induced by diesel exhaust particles (DEP) in mice. AI and AH were induced by the intratracheal instillation with 0.1 $mg/m{\ell}$ of DEP suspension once a week for 10 weeks combined with ovalbumin (OVA) sensitization. Mice were also treated orally with 75 $mg/m{\ell}$ of CGS, 5 days a week for 10 weeks. Oral CGS treatment decreased in the level of serum immunoglobulin (IgE) and histamine increased by DEP and OVA, and declined respiratory resistance. It also dropped an enhanced infiltration of eosinophils in the bronchoalveolar lavage fluid (BALF) of mice, and an increased 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 CGS may alleviate allergen-related AI and AH in mice and may play an important role in the modulation of asthmatic inflammation.

• Biomolecules & Therapeutics
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• v.19 no.4
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• pp.466-471
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• 2011

Allergic asthma is complex inflammatory airway disorder caused by genetic and environmental factors. Sulfamethoxazole, a sulfonamide, is the cause of drug rash with eosinophilia and systemic symptoms syndrome. Parasites infection also related with eosinophilia and allergic diseases. In the present study, we investigated the modulating effects of parasitic derivative and sulfamethoxazole (SMX) on allergic airway inflammation in the ovalbumin (OVA)-induced murine asthma model. Histopathological changes, cytokine secretion, and total and allergen-specific IgE were investigated. BALB/c mice were treated with Ascaris suum extract or SMX for 4 weeks before sensitized and challenged to ovalbumin. Pre-treatment of Ascaris suum extract decreased allergic inflammation in lung tissue and IL-4, total IgE, and OVA-specific IgE levels in bronchoalveolar lavage fluid. However, pre-treatment of SMX did not show any effects on allergic airway inflammation. These results indicate that parasitic infection has protective effects on allergic asthma, but the sulfamamides may not relate with allergic asthma.

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

• Tuberculosis and Respiratory Diseases
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• v.57 no.6
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• pp.543-552
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• 2004

Background : Airway remodeling of the asthmatic airway, the result of persistent inflammation in the bronchial wall, is associated with irreversible airway obstruction and the severity of asthma. Previous reports had represented that adminitering CpG-oligodeoxynucleotides (CpG-ODN) before sensitization or challenge by allergens inhibits the development of eosinophilic airway inflammation in a murine model of asthma, but the effects of CpG-ODNs on chronic inflammation and airway remodeling had not been characterized. To investigate the influence of CpG-ODNs on chronic inflammation and remodeling of the airway, we performed studies using a murine model of chronic allergen-induced asthma. Methods : Balb/C mice were sensitized to ovalbumin(OVA) and subsequently exposed to nebulized OVA by means of inhalation twice weekly for 7 weeks. CpG-ODNs($30{\mu}g$) was administered intraperitoneally at sensitization. After final inhalation, mice were evaluated for airway hyperresponsiveness, chronic airway inflammation and remodeling. Results : The mice exposed to chronic and recurrent airway challenge with OVA had persistent airway hyperresponsiveness, chronic inflammation and airway remodeling. Mice treated with CpG-ODNs exhibited decreased bronchial hyperresponsiveness, OVA-specific IgE, chronic inflammation and evidence of airway remodeling, including goblet cell hyperplasia and subepithelial fibrosis. Conclusion : CpG-ODNs was thought to prevent chronic inflammation and remodeling changes in a murine model of chronic asthma.

• Journal of Ginseng Research
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• v.45 no.6
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• pp.654-664
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• 2021

Background: Ginsenoside Rg3, isolated from Panax ginseng, has anti-inflammatory and anti-tumor activities. It is known to reduce inflammation in acute lung injury in mice, and to reduce the expression of inflammatory cytokines and COX-2 in human asthmatic airway epithelium. In this study, we attempted to determine whether ginsenoside Rg3 inhibits airway inflammation, oxidative stress, and airway hyperresponsiveness (AHR) in the lungs of asthmatic mice. We also investigated its effects on oxidative stress and the inflammatory response in tracheal epithelial cells. Methods: Asthma symptoms were induced in female BALB/c mice sensitized with ovalbumin (OVA). Mice were divided into five groups: normal controls, OVA-induced asthmatic controls, and asthmatic mice treated with ginsenoside Rg3 or prednisolone by intraperitoneal injection. Inflammatory BEAS-2B cells (human tracheal epithelial cells) treated with ginsenoside Rg3 to investigate its effects on inflammatory cytokines and oxidative responses. Results: Ginsenoside Rg3 treatment significantly reduced eosinophil infiltration, oxidative responses, airway inflammation, and AHR in the lungs of asthmatic mice. Ginsenoside Rg3 reduced Th2 cytokine and chemokine levels in bronchoalveolar lavage fluids and lung. Inflammatory BEAS-2B cells treated with ginsenoside Rg3 reduced the eotaxin and pro-inflammatory cytokine expressions, and monocyte adherence to BEAS-2B cells was significantly reduced as a result of decreased ICAM-1 expression. Furthermore, ginsenoside Rg3 reduced the expression of reactive oxygen species in inflammatory BEAS-2B cells. Conclusion: Ginsenoside Rg3 is a potential immunomodulator that can ameliorate pathological features of asthma by decreasing oxidative stress and inflammation

• Clinical and Experimental Pediatrics
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• v.49 no.6
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• pp.581-588
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• 2006

Asthma is a chronic inflammation of the airway associated with increased bronchial hyperresponsiveness that leads to recurrent episodes of cough, wheezing, breathless, chest tightness. According the recent studies, repeated airway inflammation leads to structural changes so called 'airway remodeling' and associated with decreased pulmonary function. Airway remodeling begins form the early stage of asthma and the early diagnosis and management is very important to prevent airway remodeling. Medication for asthma can be classified into acute symptom reliever and chronic controller. Short acting beta2 agonist is a well-known reliever that reduced asthma symptoms within minutes. Controllers should be taken daily as a long-term basis to control airway inflammation. Inhaled corticosteroid(ICS) is the most effective controller in current use. However, in some patients ICS monotherapy is not sufficient to control asthma. In those cases, other medications such as long acting beta2 agonist, leukotriene modifier or sustained-release theophylline should be added to ICS, which called Add-on-Therapy. Combination inhaler devices are easy to use. Oral leukotriene modifier has a good compliance especially in children. Finally, as asthma is a chronic disease, the development of on-going partnership among health care professionals, the patients, and the patients' family is necessary for the effective management of asthma.

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