• Biomolecules & Therapeutics
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• 제24권3호
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• pp.244-251
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• 2016

Understanding the developmental mechanisms of humoral immunity against intranasal antigens is essential for the development of therapeutic approaches against air-borne pathogens as well as allergen-induced pulmonary inflammation. Follicular helper T (Tfh) cells expressing CXCR5 are required for humoral immunity by providing IL-21 and ICOS costimulation to activated B cells. However, the regulation of Tfh cell responses against intranasal antigens remains unclear. Here, we found that the generation of Tfh cells and germinal center B cells in the bronchial lymph node against intranasal proteinase antigens was independent of $TGF-{\beta}$. In contrast, administration of STAT3 inhibitor STA-21 suppressed the generation of Tfh cells and germinal center B cells. Compared with wild-type OT-II T cells, STAT3-deficient OT-II T cells transferred into recipients lacking T cells not only showed significantly reduced frequency Tfh cells, but also induced diminished IgG as well as IgE specific for the intranasal antigens. Cotransfer study of wild-type OT-II and STAT3-deficient OT-II T cells revealed that the latter failed to differentiate into Tfh cells. These findings demonstrate that T cell-intrinsic STAT3 is required for the generation of Tfh cells to intranasal antigens and that targeting STAT3 might be an effective approach to ameliorate antibody-mediated pathology in the lung.

• 대한의생명과학회지
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• 제29권3호
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• pp.206-209
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• 2023

Asthma is a chronic and allergic inflammation in the lung, mainly caused by house dust mites (HDM). Recent studies have reported Der p 38 and Der f 38 (Dermatophagoides pteronyssinus and D. farinae, respectively) as crucial allergens of HDMs. This study investigates the different allergic effects of Der p 38 and Der f 38 in an asthma-like mouse model. Lung infiltration of neutrophils was induced by intranasal administration of Der p 38 and Der f 38, with stronger infiltration being observed after exposure to Der p 38. Intranasal and intraperitoneal administration of Der p 38 induced the infiltration of neutrophils and eosinophils in the lung, which was similar to the effect subsequent to Der f 38 administration. Although the number of mast cells was increased, no significant difference was obtained between the effects of both allergens. In TLR4 knockout BALB/c mice, Der p 38 and Der f 38 had no effect on the infiltration of neutrophils, eosinophils, and mast cells. Additionally, allergenicity induced by Der p 38 and Der f 38 in the basophils of Der p38+/Der f 38+ asthmatic subjects was similar, although Der f 38 presented stronger allergenicity in basophils of Der p38+/Der f 38+ allergic patients than Der p 38. These findings contribute to understanding the role of similar allergen components derived from different species in the pathogenesis of allergic diseases.

• IMMUNE NETWORK
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• 제9권5호
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• pp.179-191
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• 2009

Background: The present study examines a hypothesis that short allergen-derived peptides may shift an Aspergillus fumigatus (Afu-) specific TH2 response towards a protective TH1. Five overlapping peptides (P1-P5) derived from Asp f1, a major allergen/antigen of Afu, were evaluated for prophylactic or therapeutic efficacy in BALB/c mice. Methods: To evaluate the prophylactic efficacy, peptides were intranasally administered to naive mice and challenged with Afu-allergens/antigens. For evaluation of therapeutic efficacy, the mice were sensitized with Afu-allergens/antigens followed by intranasal administration of peptides. The groups were compared for the levels of Afu-specific antibodies in sera and splenic cytokines evaluated by ELISA. Eosinophil peroxidase activity was examined in the lung cell suspensions and lung inflammation was assessed by histopathogy. Results: Peptides P1-, P2- and P3 decreased Afu-specific IgE (84.5~98.9%) and IgG antibodies (45.7~71.6%) in comparison with Afu-sensitized mice prophylactically. P1- and P2-treated ABPA mice showed decline in Afu-specific IgE (76.4~88%) and IgG antibodies (15~54%). Increased IgG2a/IgG1 and IFN-${\gamma}$/IL-4 ratios were observed. P1-P3 prophylactically and P1 therapeutically decreased IL-5 levels and eosinophil peroxidase activity. P1 decreased inflammatory cells' infiltration in lung tissue comparable to non-challenged control. Conclusion: Asp f1-derived peptide P1, prophylactically and therapeutically administered to Balb/c mice, is effective in regulating allergic response to allergens/antigens of Afu, and may be explored for immunotherapy of allergic aspergillosis in humans.

• Clinical and Experimental Pediatrics
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• 제49권6호
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• pp.593-601
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• 2006

Allergic rhinitis is a common disease of childhood characterized by nasal, throat, and ocular itching, rhinorrhea, sneezing, nasal congestion. Those affected with allergic rhinitis often suffer from associated inflammatory conditions of the mucosa, such as allergic conjunctivitis, rhinosinusitis, asthma, otitis media with effusion, and other atopic conditions, such as eczema and food allergies. Allergic rhinitis must be diagnosed and treated properly to prevent complications and impaired quality of life. Despite a high prevalence, allergic rhinitis isoften undiagnosed and inadequately treated, especially in the pediatric population. The first step in treatment is environmental control when appropriate. It may be difficult to eliminate all offending allergens effectively to reduce symptoms, so medications are often required. Many different classes of medications are now available, and they have been shown to be effective and safe in a large number of well-designed, clinical trials. Antihistamines are effective in treating immediate symptoms of sneezing, pruritus, watery eyes, and rhinorrhea. Second generation antihistamines are the preferred antihistamines because of their superior side effect profile. Thus, decongestants are commonly used with oral antihistamines. Intranasal corticosteroids are the most effective therapy for allergic rhinitis. Leukotriene modifier may be as effective as antihistamines in treating allergic rhinitis symptoms. Cromolyn sodium is an option for mild disease when used prophylactically, and ipratropium bromide is effective when rhinorrhea is the predominant symptom. When avoidance measures and medications are not effective, specific immunotherapy is an effective alternative. Only immunotherapy results in sustained changes in the immune system. Because of improved understanding of the pathogenesis, new and better therapies may be forthcoming. The effective treatment of allergic rhinitis in children will reduce symptoms and will improve overall health and quality of life, making a happier, healthier child.

• 한방안이비인후피부과학회지
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• 제18권3호
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• pp.26-36
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• 2005

Objectives: Maier symptoms of allergic rhinitis are nasal obstructions, sneezing and watery rhinorrhea. When exposed to certain allergens, the IgE covered mast cells degranulate and release inflammatory mediators and cytokines which result in a local inflammatory reaction. In many recent studies, molecular biological methods have been used to investigate the role of cytokines in pathogenesis and new therapeutic targets of allergic rhinitis. This experimental study was done to reveal the effects of the Bojungikgi-tang on the allergic rhinitis. We have studied effect of mice on OVA-induced production of IL-4, IL-5, $INF-{\gamma}$ by murine splenocytes and effect of OVA-induced Total IgE and OVA-specific IgE Meterial and Metheds: 21 BALB/c rats were divided into three groups: normal group, control group, experimental group. To induce the allergic rhinitis in control group and experimental group, rats were sentitized intraperitioneally with 0.1% ovalbumin solution 3 times at intervals of 2 weeks. Then intranasal sensitization was performed by diffusing 0.1% ovalbumin solution 3 times at intervals of 2 days for a week. After that time, rats in experimental group were oral administration treated by the Bojuogikgi-tang fer 28 days. We observed changes of IL-4, IL-5, $INF-{\gamma}$, Total IgE and OVA-specific IgE. We used independent-test statistically. Results: 1. In IL-4 study, Bojungikgi-tang treated group didn't show significant differences. 2. In IL-5 study, Bojungikgi-tang treated group shows significant differences. 3. In $INF-{\gamma}$ study, Bojungikgi-tang treated group shows significant differences. 4. In Total IgE, Bojungikgi-tang treated group shows significant differences. 5. In OVA-specific IgE, Bojungikgi-tang treated group didn't show significant differences. According to this result, Bojungikgi-tang was concluded to be effective on lowering the total IgE. Through this. Bojungikgi tang seems to reduce the symptoms of allergic rhinitis. More studies are required to know exact mechanism of Bojungikgi tang to show the anti allergenic effect.

• Clinical and Experimental Pediatrics
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• 제53권4호
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• pp.481-487
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• 2010

목 적: 최근 여러 연구결과 천식을 포함한 알레르기질환의 발병에 소아 성장시기에 알레르겐이나 내독소(LPS)등과 같은 물질에 노출이 중요한 역할을 하는 것으로 제시되었다. 이에 연구자들은 출생 초기에 기도 점막을 통한 알레르겐과 내독소에의 노출이 성장한 후에 알레르기 기도염증과 과반응성의 발생에 미치는 효과를 생쥐 모델을 통하여 규명하고자 본 연구를 시행하였다. 방 법: 실험동물은 무균 상태의 생후 1주이내의 암컷 BALB/c 생쥐를 사용하였다. 실험동물들에게는 각각 신생생쥐시기에 생리식염수, 1% ovalbumin (OVA), $1.0{\mu}g$ LPS, $1.0{\mu}g$ LPS in 1% OVA를 각 비공을 통하여 투여하였다. 실험동물은 연구 시작 제 35일부터 10일간 5% OVA로 감작시켰으며 최종 기도 감작 10일 후부터 3일간 1% OVA로 기도 항원유발을 시행하였다. 최종 기도유발 48시간 후 체적검사(plethysmography)를 이용하여 비특이적 기도과반응성 검사(Methcholine challenge test)를 시행하였으며 검사 후 실험동물을 희생시켜 검체를 취하여 BAL액내 세포분획, 사이토카인, 혈청 면역글로불린을 측정하였다. 결 과: 1) 메타콜린에 의한 기도과반응성은 생후 초기에 OVA, LPS, OVA/LPS를 투여한 군에서 생리식염수를 투여한 군에 비해 통계적으로 유의하게 억제되었다. 2) OVA, LPS, OVA/LPS를 투여한 군에서 BAL 액내의 호산구수와 IL-4, IL-5가 유의하게 낮았다. 3) 혈청내 OVA 특이 IgE는 OVA, LPS, OVA/LPS 투여군에서 유의하게 감소되었다. 결 론: 본 연구 결과 신생생쥐 시기의 점막을 통한 항원, 내독소의 노출이 성숙한 후 항원에 의한 기도염증 및 과반응성의 발생을 억제하였으며 향후 이러한 효과의 작용기전에 대한 연구가 필요할 것으로 생각한다.