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Protease-Activated Receptors 2-Antagonist Suppresses Asthma by Inhibiting Reactive Oxygen Species-Thymic Stromal Lymphopoietin Inflammation and Epithelial Tight Junction Degradation.

Abstract

PURPOSE

Protease-activated receptor 2 (PAR2) reportedly triggers the immune response in allergic asthma. We aimed to investigate the mechanism on allergic inflammation mediated by PAR2.

METHODS

Human lung epithelial cells (A549 cells) were used for in vitro, and the German cockroach extract (GCE)-induced mouse model was developed for in vivo studies.

RESULTS

In A549 cells, the levels of reactive oxygen species (ROS) and thymic stromal lymphopoietin (TSLP) were significantly increased by GCE treatment, but were suppressed by PAR2-antagonist (PAR2-ant) or N-acetylcysteine (NAC) treatment. Claudin-1 was degraded by GCE, and was restored by PAR2-ant or NAC in the cells. In the mouse model, the clinical appearance including bronchial hyperresponsiveness, bronchoalveolar lavage fluid analysis and total immunoglobulin E were significantly suppressed by PAR2-ant or NAC. Moreover, TSLP levels in the lung were suppressed by the same treatments in the lung. Claudin-1 was also degraded by GCE, and was restored by PAR2-ant or NAC.

CONCLUSIONS

ROS generation and epidermal tight junction degradation are triggered by protease, followed by the induction of TSLP in allergic asthma. Our findings could suggest that PAR2-ant or anti-oxidants could be considered for allergic diseases as preventive alternatives.

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  • Authors+Show Affiliations

    ,

    Department of Internal Medicine, Chonnam National University College of Veterinary Medicine, Gwangju, Korea.

    ,

    Asan Institute for Life Sciences, University of Ulsan College of Medicine, Seoul, Korea.

    ,

    CRID Center, NeoPharm Co., Ltd., Daejeon, Korea.

    Department of Pediatrics, Childhood Asthma Atopy Center, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea. Environmental Health Center, Asan Medical Center, Seoul, Korea. sjhong@amc.seoul.kr.

    Source

    Allergy, asthma & immunology research 11:4 2019 Jul pg 560-571

    Pub Type(s)

    Journal Article

    Language

    eng

    PubMed ID

    31172724

    Citation

    Kim, Ha Jung, et al. "Protease-Activated Receptors 2-Antagonist Suppresses Asthma By Inhibiting Reactive Oxygen Species-Thymic Stromal Lymphopoietin Inflammation and Epithelial Tight Junction Degradation." Allergy, Asthma & Immunology Research, vol. 11, no. 4, 2019, pp. 560-571.
    Kim HJ, Lee SH, Jeong S, et al. Protease-Activated Receptors 2-Antagonist Suppresses Asthma by Inhibiting Reactive Oxygen Species-Thymic Stromal Lymphopoietin Inflammation and Epithelial Tight Junction Degradation. Allergy Asthma Immunol Res. 2019;11(4):560-571.
    Kim, H. J., Lee, S. H., Jeong, S., & Hong, S. J. (2019). Protease-Activated Receptors 2-Antagonist Suppresses Asthma by Inhibiting Reactive Oxygen Species-Thymic Stromal Lymphopoietin Inflammation and Epithelial Tight Junction Degradation. Allergy, Asthma & Immunology Research, 11(4), pp. 560-571. doi:10.4168/aair.2019.11.4.560.
    Kim HJ, et al. Protease-Activated Receptors 2-Antagonist Suppresses Asthma By Inhibiting Reactive Oxygen Species-Thymic Stromal Lymphopoietin Inflammation and Epithelial Tight Junction Degradation. Allergy Asthma Immunol Res. 2019;11(4):560-571. PubMed PMID: 31172724.
    * Article titles in AMA citation format should be in sentence-case
    TY - JOUR T1 - Protease-Activated Receptors 2-Antagonist Suppresses Asthma by Inhibiting Reactive Oxygen Species-Thymic Stromal Lymphopoietin Inflammation and Epithelial Tight Junction Degradation. AU - Kim,Ha Jung, AU - Lee,Seung Hwa, AU - Jeong,Sekyoo, AU - Hong,Soo Jong, PY - 2018/09/25/received PY - 2019/02/10/revised PY - 2019/02/12/accepted PY - 2019/6/8/entrez PY - 2019/6/7/pubmed PY - 2019/6/7/medline KW - Asthma KW - protease-activated receptor 2 KW - reactive oxygen species KW - thymic stromal lymphopoietin KW - tight junction SP - 560 EP - 571 JF - Allergy, asthma & immunology research JO - Allergy Asthma Immunol Res VL - 11 IS - 4 N2 - PURPOSE: Protease-activated receptor 2 (PAR2) reportedly triggers the immune response in allergic asthma. We aimed to investigate the mechanism on allergic inflammation mediated by PAR2. METHODS: Human lung epithelial cells (A549 cells) were used for in vitro, and the German cockroach extract (GCE)-induced mouse model was developed for in vivo studies. RESULTS: In A549 cells, the levels of reactive oxygen species (ROS) and thymic stromal lymphopoietin (TSLP) were significantly increased by GCE treatment, but were suppressed by PAR2-antagonist (PAR2-ant) or N-acetylcysteine (NAC) treatment. Claudin-1 was degraded by GCE, and was restored by PAR2-ant or NAC in the cells. In the mouse model, the clinical appearance including bronchial hyperresponsiveness, bronchoalveolar lavage fluid analysis and total immunoglobulin E were significantly suppressed by PAR2-ant or NAC. Moreover, TSLP levels in the lung were suppressed by the same treatments in the lung. Claudin-1 was also degraded by GCE, and was restored by PAR2-ant or NAC. CONCLUSIONS: ROS generation and epidermal tight junction degradation are triggered by protease, followed by the induction of TSLP in allergic asthma. Our findings could suggest that PAR2-ant or anti-oxidants could be considered for allergic diseases as preventive alternatives. SN - 2092-7355 UR - https://www.unboundmedicine.com/medline/citation/31172724/Protease-Activated_Receptors_2-Antagonist_Suppresses_Asthma_by_Inhibiting_Reactive_Oxygen_Species-Thymic_Stromal_Lymphopoietin_Inflammation_and_Epithelial_Tight_Junction_Degradation L2 - https://e-aair.org/DOIx.php?id=10.4168/aair.2019.11.4.560 DB - PRIME DP - Unbound Medicine ER -