3061 PAR2-Antagonist Suppresses Protease-Induced Allergic Inflammation Mediated By Degradation of Lung Epithelial Tight Junction and Generation of ROS

Friday, 16 October 2015
Hall D1 Foyer (Floor 3) (Coex Convention Center)

Ha-Jung Kim , Asan Institute for Life Sciences, Seoul, South Korea

Young-Joon Kim , Asan Institute for Life Sciences, Seoul, South Korea

Bok Kyoung Jung , Asan Institute for Life Sciences, Seoul, South Korea

Seung-Hwa Lee , Asan Institute for Life Sciences, Seoul, South Korea

Mi-Jin Kang, MS , Asan Institute for Life Sciences, Seoul, South Korea

Sekyoo Jeong , Neopharm Co., Ltd, Seoul, South Korea

Eun Lee, MD , Asan Medical Center, Seoul, South Korea

Hyun-Ju Cho, MD , Department of Pediatrics, Childhood Asthma Atopy Center, Enviromental Health Center, University of Ulsan College of Medicine,, Asan Medical Center, Seoul, South Korea

Young-Ho Kim, MD , Department of Pediatrics, Childhood Asthma Atopy Center, Enviromental Health Center, University of Ulsan College of Medicine,, Asan Medical Center, Seoul, South Korea

Song-I Yang, MD , Department of Pediatrics, Hallym University Sacred Heart Hospital, Anyang, South Korea

Seo Hee Kim , Asan Medical Center, Seoul, South Korea

Soo-Jong Hong, MD, PhD , Department of Pediatrics, Childhood Asthma Atopy Center, Enviromental Health Center, University of Ulsan College of Medicine,, Asan Medical Center, Seoul, South Korea

Background: Protease in the common allergens (e.g., cockroach, mold) can induce a pathogenesis on allergic diseases. Protease activated receptor 2 (PAR2) is reported to trigger immune response on allergic asthma.

Aim: This study aimed to investigate the effects of a PAR2-antagonist on protease-induced allergic inflammation and identify the mechanism.

Methods: PAR2-antagonist was administered intranasally in the mouse model of asthma induced by German cockroach extract (GCE). In addition, human lung epithelial cells (A549 cells) were treated with GCE, PAR2-antagonist, and NAC to confirm the mechanism related in the vivo results.

Results: Airway hyperresponsiveness, total IgE production, and pulmonary inflammation were significantly suppressed by NAC and the PAR2-antagonist in the mouse model. Th2-cytokines and TSLP in the lung were suppressed by the NAC and PAR-2 antagonist. Tight junction protein, claudin-1 was disturbed by GCE and restored by PAR2-antagonist and NAC in the lung. TSLP and claudin-1 showed the same correlation in the human lung epithelial cells by the two in vitro.

Conclusions: GCE elicits allergic inflammation mediated by disruption of tight junction triggered by PAR2 and generation of ROS.