국내 유래 집먼지진드기 알레르겐을 이용한 알레르겐 만성노출 실험동물모델 구축
Establishment of a murine model based on chronic exposure to domestic house dust mites in Korea
2
조회
0
다운로드
0
인용
0
참고문헌
키워드
초록
Purpose: Asthma is a chronic disorder characterized by bronchial hyperresponsiveness and reversible airflow obstruction. Repeated exposure to allergens of the respiratory tract causes chronic inflammation, followed by structural changes in the lung called airway remodeling. House dust mites (HDM) are known as the predominant inhalant allergens, and several studies have reported that the allergenic property of HDM extracts varied with the geographic regions where they were produced. This study aimed to establish a murine experimental model by long-term intranasal exposure to HDM allergen indigenous to Korea. Methods: HDM extracts from cultured Dermatophagoides pteronissunus in Korea were used in our model. We administered the extracts intranasally to BALB/c mice 3 times a week for 8 or 10 consecutive weeks, followed by measuring airway allergic inflammation and airway remodeling. Results: The number of neutrophils in the lungs was higher in the group with long-term exposure to HDM than in the normal control group. The levels of total IgE and a wide range of cytokines, including Th1/Th2/Th17 and proinflammatory cytokines, were significantly higher in the long-term HDM-exposed group than in the normal control group. The development of airway remodeling by chronic exposure to HDM was observed by measuring diverse factors, including collagens and transforming growth factor (TGF)-β. These significant results were more clearly shown in the group exposed to HDM for 8 weeks than 10 weeks. Conclusion: A murine model of chronic exposure to domestic HDM in Korea was successfully established. We suggest that our model may be helpful in the research into asthma with airway remodeling.
Abstract
Purpose: Asthma is a chronic disorder characterized by bronchial hyperresponsiveness and reversible airflow obstruction. Repeated exposure to allergens of the respiratory tract causes chronic inflammation, followed by structural changes in the lung called airway remodeling. House dust mites (HDM) are known as the predominant inhalant allergens, and several studies have reported that the allergenic property of HDM extracts varied with the geographic regions where they were produced. This study aimed to establish a murine experimental model by long-term intranasal exposure to HDM allergen indigenous to Korea. Methods: HDM extracts from cultured Dermatophagoides pteronissunus in Korea were used in our model. We administered the extracts intranasally to BALB/c mice 3 times a week for 8 or 10 consecutive weeks, followed by measuring airway allergic inflammation and airway remodeling. Results: The number of neutrophils in the lungs was higher in the group with long-term exposure to HDM than in the normal control group. The levels of total IgE and a wide range of cytokines, including Th1/Th2/Th17 and proinflammatory cytokines, were significantly higher in the long-term HDM-exposed group than in the normal control group. The development of airway remodeling by chronic exposure to HDM was observed by measuring diverse factors, including collagens and transforming growth factor (TGF)-β. These significant results were more clearly shown in the group exposed to HDM for 8 weeks than 10 weeks. Conclusion: A murine model of chronic exposure to domestic HDM in Korea was successfully established. We suggest that our model may be helpful in the research into asthma with airway remodeling.
참고문헌 (28)
- Papi A, "Asthma", Lancet, 391, pp.783~800 (2018)
- Eun-young Lee, "Increasing Prevalence and Mortality of Asthma With Age in Korea, 2002–2015: A Nationwide, Population-Based Study", Allergy, Asthma & Immunology Research, 12(3), pp.467~484 (2020), 대한천식알레르기학회
- Kuruvilla ME, "Epidemiology and risk factors for asthma", Respir Med, 149, pp.16~22 (2019)
- Galli SJ, "The development of allergic inflammation", Nature, 454, pp.445~454 (2008)
- Locksley RM, "Asthma and allergic inflammation", Cell, 140, pp.777~783 (2010)
- Lambrecht BN, "The cytokines of asthma", Immunity, 50, pp.975~991 (2019)
- Lambrecht BN, "The airway epithelium in asthma", Nat Med, 18, pp.684~692 (2012)
- Boulet LP, "Airway remodeling in asthma : update on mechanisms and therapeutic approaches", Curr Opin Pulm Med, 24, pp.56~62 (2018)
- Johnson JR, "Continuous exposure to house dust mite elicits chronic airway inflammation and structural remodeling", Am J Respir Crit Care Med, 169, pp.378~385 (2004)
- Chen ZG, "Neutralization of TSLP inhibits airway remodeling in a murine model of allergic asthma induced by chronic exposure to house dust mite", PLoS One, 8, pp.e51268~ (2013)
- Woo LN, "A 4-week model of house dust mite(HDM)induced allergic airways inflammation with airway remodeling", Sci Rep, 8, pp.6925~ (2018)
- Park SC, "Geographic and demographic variations of inhalant allergen sensitization in Koreans and non-Koreans", Allergol Int, 68, pp.68~76 (2019)
- Zock JP, "Distribution and determinants of house dust mite allergens in Europe : the European Community Respiratory Health Survey II", J Allergy Clin Immunol, 118, pp.682~690 (2006)
- 정경용, "Standardization of House Dust Mite Extracts in Korea", Allergy, Asthma & Immunology Research, 4(6), pp.346~350 (2012), 대한천식알레르기학회
- Bracken SJ, "Long-term exposure to house dust mite leads to the suppression of allergic airway disease despite persistent lung inflammation", Int Arch Allergy Immunol, 166, pp.243~258 (2015)
- Simeone-Penney MC, "Airway epithelial STAT3 is required for allergic inflammation in a murine model of asthma", J Immunol, 178, pp.6191~6199 (2007)
- Hough KP, "Airway remodeling in asthma", Front Med(Lausanne), 7, pp.191~ (2020)
- Vroman H, "Development of eosinophilic inflammation is independent of B-T cell interaction in a chronic house dust mite-driven asthma model", Clin Exp Allergy, 47, pp.551~564 (2017)
- Chen J, "Therapeutic effects of resveratrol in a mouse model of HDM-induced allergic asthma", Int Immunopharmacol, 25, pp.43~48 (2015)
- 김지태, "Comparison of Allergenic Properties among Commercially Available House Dust Mite Allergen Extracts in Korea", Yonsei Medical Journal, 62(1), pp.86~90 (2021), 연세대학교의과대학[DOI]
- Nakayama T, "Introduction to"allergic inflammation"", Immunol Rev, 278, pp.5~7 (2017)
- Cosmi L, "Th17 cells : new players in asthma pathogenesis", Allergy, 66, pp.989~998 (2011)
- Newcomb DC, "Th17-mediated inflammation in asthma", Curr Opin Immunol, 25, pp.755~760 (2013)
- Samitas K, "Upper and lower airway remodelling mechanisms in asthma, allergic rhinitis and chronic rhinosinusitis : the one airway concept revisited", Allergy, 73, pp.993~1002 (2018)
- Fehrenbach H, "Airway remodeling in asthma : what really matters", Cell Tissue Res, 367, pp.551~569 (2017)
- Rogovskii V, "Immune tolerance as the physiologic counterpart of chronic inflammation", Front Immunol, 11, pp.2061~ (2020)
- Nials AT, "Mouse models of allergic asthma : acute and chronic allergen challenge", Dis Model Mech, 1, pp.213~220 (2008)
- Cyphert-Daly JM, "Physiologic response to chronic house dust mite exposure in mice is dependent on lot characteristics", J Allergy Clin Immunol, 144, pp.1428~1432 (2019)