• IMMUNE NETWORK
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• 제14권5호
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• pp.249-254
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• 2014

Allergic asthma is a chronic pulmonary inflammatory disease characterized by reversible airway obstruction, hyperresponsiveness and eosinophils infiltration. Toll-like receptors (TLRs) signaling are closely associated with asthma and have emerged as a novel therapeutic target in allergic disease. The functions of TLR3 and TLR4 in allergic airway inflammation have been studied; however, the precise role of TIR-domain-containing adapter-inducing interferon-${\beta}$ (TRIF), the adaptor molecule for both TLR3 and TLR4, is not yet fully understood. To investigate this, we developed a mouse model of OVA-induced allergic airway inflammation and compared the severity of allergic airway inflammation in WT and $TRIF^-/^-$ mice. Histopathological assessment revealed that the severity of inflammation in airway inflammation in TRIF-deficient mice was comparable to that in WT mice. The total number of cells recovered from bronchoalveolar lavage fluid did not differ between WT and TRIF-deficient mice. Moreover, TRIF deficiency did not affect Th1 and Th2 cytokine production in lung tissue nor the level of serum OVA-specific IgE, $IgG_1$ and $IgG_{2c}$. These findings suggest that TRIF-mediated signaling may not be critical for the development of allergic airway inflammation.

• Biomolecules & Therapeutics
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• 제19권4호
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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.

• BMB Reports
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• 제54권3호
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• pp.182-187
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• 2021

Leukotriene B4 (LTB4) is a lipid mediator of inflammation that is generated from arachidonic acid via the 5-lipoxygenase pathway. Previous studies have reported that the receptors of LTB4, BLT1, and BLT2 play mediatory roles in the allergic airway inflammation induced by ovalbumin (OVA). However, considering that house dust mites (HDMs) are the most prevalent allergen and well-known risk factor for asthmatic allergies, we are interested in elucidating the contributory roles of BLT1/2 in HDM-induced allergic airway inflammation. Our aim in this study was to investigate whether BLT1/2 play any roles in HDM-induced allergic airway inflammation. In this study, we observed that the levels of ligands for BLT1/2 [LTB4 and 12(S)-HETE (12(S)-hydroxyeicosatetraenoic acid)] were significantly increased in bronchoalveolar lavage fluid (BALF) after HDM challenge. Blockade of BLT1 or BLT2 as well as of 5-lipoxygenase (5-LO) or 12-lipoxygenase (12-LO) markedly suppressed the production of TH2 cytokines (IL-4, IL-5, and IL-13) and alleviated lung inflammation and mucus secretion in an HDM-induced eosinophilic airway-inflammation mouse model. Together, these results indicate that the 5-/12-LO-BLT1/2 cascade plays a role in HDM-induced airway inflammation by mediating the production of TH2 cytokines. Our findings suggest that BLT1/2 may be a potential therapeutic target for patients with HDM-induced allergic asthma.

• BMB Reports
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• 제52권4호
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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.

• 대한본초학회지
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• 제26권4호
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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.

• IMMUNE NETWORK
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• 제11권3호
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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.

• Parasites, Hosts and Diseases
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• 제60권4호
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• pp.229-239
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• 2022

The high percentage of Vermamoeba was found in tap water in Korea. This study investigated whether Vermamoeba induced allergic airway inflammation in mice. We selected 2 free-living amoebas (FLAs) isolated from tap water, which included Korean FLA 5 (KFA5; Vermamoeba vermiformis) and 21 (an homolog of Acanthamoeba lugdunensis KA/E2). We axenically cultured KFA5 and KFA21. We applied approximately 1×10⁶ to mice's nasal passages 6 times and investigated their pathogenicity. The airway resistance value was significantly increased after KFA5 and KFA21 treatments. The eosinophil recruitment and goblet cell hyperplasia were concomitantly observed in bronchial alveolar lavage (BAL) fluid and lung tissue in mice infected with KFA5 and KFA21. These infections also activated the Th2-related interleukin 25, thymic stromal lymphopoietin, and thymus and activation-regulated chemokines gene expression in mouse lung epithelial cells. The CD4⁺ interleukin 4⁺ cell population was increased in the lung, and the secretion of Th2-, Th17-, and Th1-associated cytokines were upregulated during KFA5 and KFA21 infection in the spleen, lung-draining lymph nodes, and BAL fluid. The pathogenicity (allergenicity) of KFA5 and KFA21 might not have drastically changed during the long-term in vitro culture. Our results suggested that Vermamoeba could elicit allergic airway inflammation and may be an airway allergen.

• Clinical and Experimental Pediatrics
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• 제54권9호
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• pp.373-379
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• 2011

Purpose: 4-1BB (CD 137) is a costimulatory molecule expressed on activated T-cells. Repression by 4-1BB is thought to attenuate Th2-mediated allergic reactions. The aim of this study was to investigate the effect of 4-1BB on allergic airway inflammation in a murine asthma model. Methods: BALB/c mice were sensitized to and challenged with ovalbumin (OVA). Hu.4-1BB-Fc was administered 1 day before the first OVA sensitization or 1 day after the second OVA sensitization. Following antigen challenge, airway responsiveness to methacholine was assessed and bronchoalveolar lavage (BAL) fluid was analyzed. Total immunoglobulin (Ig) E, OVA-specific IgE, $IgG_1$, and $IgG_{2a}$ levels in sera were measured by enzyme-linked immunosorbent assay. Lung pathology was also evaluated. Results: In mice treated with Hu.4-1BB-Fc before the first OVA sensitization, there was a marked decrease in airway hyperresponsiveness, total cell count, and eosinophil count in the BAL fluid. In addition, Hu.4-1BB-Fc treatment decreased serum OVA-specific $IgG_1$ levels and increased serum $IgG_{2a}$ level significantly compared with the corresponding levels in mice sensitized to and challenged with OVA. Hu.4-1BB-Fc-treated mice also showed suppressed peribronchial and perivascular inflammatory cell infiltration. In contrast, treatment with Hu.4-1BB-Fc 1 day after sensitization had no effect on airway hyperresponsiveness and showed less suppression of inflammation in lung tissue. Conclusion: Administration of Hu.4-1BB-Fc can attenuate airway inflammation and hyperreactivity in a mouse model of allergic airway inflammation. In addition, administration before sensitization may be more effective. These findings suggest that 4-1BB may be a useful therapeutic molecule against asthma.

• 동의생리병리학회지
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• 제20권6호
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• pp.1636-1648
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• 2006

There are detailed descriptions of the clinical experiences and prescriptions of asthma in traditional Korean medicine. Zedoariae rhizoma is one of the Korean herbal medicines used to treat bronchial asthma and allergic rhinitis for centuries. However, the therapeutic mechanisms of this medication are still far from clear, In this study, a house-dust-mite (Dermatophagoides pteronyssinus [Der p])-sensitized murine model of asthma was used to evaluate the immunomodulatory effect of Zedoariae rhizoma on the allergen-induced airway inflammation in asthma. Three different protocols were designed to evaluate the treatment and/or long-term prophylacitic effect of Zedoariae rhizoma in Der p-sensitized mice. Cellular infiltration and T-cell subsets in the bronchoalveolar lavage fluid (BALF)of allergen-challenged mice were analyzed. Intrapulmonary lymphocytes were also isolated to evaluate their response to allergen stimulation. When Zedoariae rhizoma was administered to the sensitized mice before AC (groups A and C), it suppressed airway inflammation by decreasing the number of total cells and eosinophil infiltration in the BALF, and downregulated the allergen- or mitogen-induced intrapulmonary lymphocyte response of sensitized mice as compared to those of controls. This immunomodulatory effect of Zedoariae rhizoma may be exerted through the regulation of T-cell subsets by elevation or activation of the CD8+ and double-negative T-cell population in the lung. However, the administration of Zedoariae rhizoma to sensitized mice 24 h after AC (group B) did not have the same inhibitory effect on the airway inflammation as Zedoariae rhizoma given before AC. Thus, the administration of Zedoariae rhizoma before AC has the immunomodulatory effect of reducing bronchial inflammation in the allergen-sensitized mice. On the other hand, to determine the potentiality of prophylactic and/or therapeutic approaches using a traditional herbal medicine, Zedoariae rhizoma, for the control of allergic disease, we examined the effects of oral administration of Zedoariae rhizoma on a murine model of asthma allergic responses. When oral administration of Zedoariae rhizoma was begun at the induction phase immediately after OVA sensitization, eosinophilia and Th2-type cytokine production in the airway were reduced in OVA-sensitized mice following OVA inhalation. These results suggest that the oral administration of Zedoariae rhizoma dichotomously modulates allergic inflammation in murine model for asthma, thus offering a different approach for the treatment of allergic disorders.

• 한방안이비인후피부과학회지
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• 제20권1호통권32호
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• pp.177-194
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• 2007

Fructus of Rubus coreanus $M_{IQ.}$. (FRCM) has been used for stuttering urination, prostate gland disease, and impotence in Korean traditional medicine. Water extract of FRCM (WFRCM) treatment significantly attenuated airway hyperreactivity (AHR). Airway recruitment of leukocytes and eosinophils was also markedly reduced by WFRCM administration, suggesting that WFRCM can alleviate the airway inflammation. However, the level of cytokine (IL-4, IL-5, and IL-13) in bronchoalveolar lavage fluid (BALF) and lung was not different compared with positive control. WFRCM reduced the number of draining lymph node cells during OVA-induced allergic asthma. I further examined transcription level of cytokine in lung. WFRCM treatment reduced IL-4 and IL-13 mRNA in lung and inhibited IgE and IgG1 but not IgG2a. My data suggest that WFRCM attenuates OVA-induced allergic asthma through inhibition of Th2 cell response.