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

Hyun Jin Min, Joon Soon Park, Kyung Soo Kim, Seung Yong Park, Honghwan Choi, Ju Hee Seo, Miran Kang, Joo Heon Yoon, Chang Hoon Kim, Sehoon Kim, Hyung Ju Cho

Research output: Contribution to journalArticlepeer-review

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.

Original languageEnglish
Pages (from-to)483-494
Number of pages12
JournalClinical Science
Volume135
Issue number3
DOIs
Publication statusPublished - 2021 Feb

Bibliographical note

Funding Information:
This work was supported by the National Research Foundation of Korea (NRF) grant funded by the Korean government [grant number NRF-2017R1A1A1A05000760 (to Hyun Jin Min)]; the Basic Science Research Program through the NRF of Korea funded by the Ministry of Education [grant number NRF-2018R1D1A1A02049236 (to Hyung-Ju Cho)]; the Faculty Research Grant from the Yonsei University College of Medicine [grant number 6-2018-0167]; and the Korea Research Institute of Standards and Science for the KIST Intramural Program [grant number KRISS-2020-GP2020-0004 (to Sehoon Kim)].

Publisher Copyright:
© 2021 Portland Press Ltd. All rights reserved.

All Science Journal Classification (ASJC) codes

  • Medicine(all)

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