Th2 cytokines-DUOX2-ROS-HMGB1 translocation axis is important in the pathogenesis of allergic rhinitis.

Affiliation

Min HJ(1), Park JS(1), Kim KS(1), Park SY(1), Choi H(2), Seo JH(3)(4), Kang M(3)(4), Yoon JH(3)(4), Kim CH(3)(4), Kim S(5)(6), Cho HJ(3)(4).
Author information:
(1)Department of Otorhinolaryngology-Head and Neck Surgery, Chung-Ang University College of Medicine, Seoul, Republic of Korea.
(2)Division of Chemical Engineering, Konkuk University, Seoul, Republic of Korea.
(3)The Airway Mucus Institute, Yonsei University College of Medicine, Seoul, Republic of Korea.
(4)Department of Otorhinolaryngology, Yonsei University College of Medicine, Seoul, Republic of Korea.
(5)Center for Theragnosis, Korea Institute of Science and Technology, Seoul, Republic of Korea.
(6)KU-KIST Graduate School of Converging Science and Technology, Korea University, Seoul, Republic of Korea.

Abstract

The function of high-mobility group box 1 (HMGB1) varies according to its location. However, the translocation mechanism behind HMGB1 remains unclear. We hypothesize that type 2 helper T cell (Th2) cytokines are involved in the translocation of HMGB1 in the upper airway epithelium. We investigated the mechanism behind HMGB1 translocation using Th2 cytokine stimulation and examined the clinical significance of HMGB1 translocation in allergic rhinitis (AR). Cytoplasmic and extracellular HMGB1 were increased in AR. Inhibiting HMGB1 translocation with glycyrrhizic acid (GA) decreased the level of antigen-specific immunoglobulin E (IgE), the degree of Periodic Acid-Schiff (PAS), and Sirius Red staining in the murine model. The in vivo reactive oxygen species (ROS) level in the nasal mucosa was higher in the mice with AR than in the controls. Th2 cytokine-induced up-regulation of the ROS and translocation of HMGB1 by Th2 cytokines was dependent on the generated ROS. The ROS level also increased in the murine model. We suggest that the Th2 cytokine-dual oxidase (DUOX)2-ROS-HMGB1 translocation axis is important in AR pathogenesis.