Protease-Activated Receptors 2-Antagonist Suppresses Asthma by Inhibiting Reactive Oxygen Species-Thymic Stromal Lymphopoietin Inflammation and Epithelial Tight Junction Degradation.
PURPOSEProtease-activated receptor 2 (PAR2) reportedly triggers the immune response in allergic asthma. We aimed to investigate the mechanism on allergic inflammation mediated by PAR2.
METHODSHuman 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.
RESULTSIn 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.
CONCLUSIONSROS 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.
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. firstname.lastname@example.org.
Pub Type(s)Journal Article