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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
- Source :
- Allergy, Asthma & Immunology Research
- Publication Year :
- 2019
- Publisher :
- The Korean Academy of Asthma, Allergy and Clinical Immunology; The Korean Academy of Pediatric Allergy and Respiratory Disease, 2019.
-
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.
- Subjects :
- Pulmonary and Respiratory Medicine
Thymic stromal lymphopoietin
tight junction
Immunology
Inflammation
Allergic inflammation
03 medical and health sciences
0302 clinical medicine
Immune system
thymic stromal lymphopoietin
medicine
Immunology and Allergy
030223 otorhinolaryngology
Protease-activated receptor 2
A549 cell
chemistry.chemical_classification
reactive oxygen species
Reactive oxygen species
medicine.diagnostic_test
business.industry
Asthma
respiratory tract diseases
Bronchoalveolar lavage
030228 respiratory system
chemistry
Cancer research
protease-activated receptor 2
Original Article
medicine.symptom
business
Subjects
Details
- Language :
- English
- ISSN :
- 20927363 and 20927355
- Volume :
- 11
- Issue :
- 4
- Database :
- OpenAIRE
- Journal :
- Allergy, Asthma & Immunology Research
- Accession number :
- edsair.doi.dedup.....014568e0e9e32a7749c578feb792b85d