Protease-Activated Receptors 2-Antagonist Suppresses Asthma by Inhibiting Reactive Oxygen Species-Thymic Stromal Lymphopoietin Inflammation and Epithelial Tight Junction Degradation
10.4168/aair.2019.11.4.560
- Author:
Ha Jung KIM
1
;
Seung Hwa LEE
;
Sekyoo JEONG
;
Soo Jong HONG
Author Information
1. Department of Internal Medicine, Chonnam National University College of Veterinary Medicine, Gwangju, Korea.
- Publication Type:Original Article
- Keywords:
Asthma;
protease-activated receptor 2;
thymic stromal lymphopoietin;
tight junction;
reactive oxygen species
- MeSH:
Acetylcysteine;
Animals;
Asthma;
Blattellidae;
Bronchoalveolar Lavage Fluid;
Claudin-1;
Epithelial Cells;
Humans;
Immunoglobulin E;
Immunoglobulins;
In Vitro Techniques;
Inflammation;
Lung;
Mice;
Oxygen;
Reactive Oxygen Species;
Receptor, PAR-2;
Receptors, Proteinase-Activated;
Tight Junctions
- From:Allergy, Asthma & Immunology Research
2019;11(4):560-571
- CountryRepublic of Korea
- Language:English
-
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.
