4.7 Article

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

期刊

CLINICAL SCIENCE
卷 135, 期 3, 页码 483-494

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PORTLAND PRESS LTD
DOI: 10.1042/CS20201212

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资金

  1. National Research Foundation of Korea (NRF) - Korean government [NRF-2017R1A1A1A05000760]
  2. Basic Science Research Program through the NRF of Korea - Ministry of Education [NRF-2018R1D1A1A02049236]
  3. Yonsei University College of Medicine [6-2018-0167]
  4. Korea Research Institute of Standards and Science [KRISS-2020-GP2020-0004]

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The function of HMGB1 varies according to its location, and the mechanism behind its translocation remains unclear. Th2 cytokines play a role in the translocation of HMGB1 in the upper airway epithelium. The up-regulation of ROS induced by Th2 cytokines and the subsequent translocation of HMGB1 are important in the pathogenesis of allergic rhinitis.
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.

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