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ROS-dependent HMGB1 secretion upregulates IL-8 in upper airway epithelial cells under hypoxic condition

Authors
 HJ Min  ;  J-H Kim  ;  JE Yoo  ;  J-H Oh  ;  KS Kim  ;  J-H Yoon  ;  C-H Kim 
Citation
 MUCOSAL IMMUNOLOGY, Vol.10(3) : 685-694, 2017 
Journal Title
 MUCOSAL IMMUNOLOGY 
ISSN
 1933-0219 
Issue Date
2017
MeSH
Adult ; Cells, Cultured ; Chronic Disease ; Dual Oxidases/metabolism ; Female ; HMGB1 Protein/metabolism ; Humans ; Hypoxia/immunology ; Interleukin-8/genetics ; Interleukin-8/metabolism ; Male ; Middle Aged ; Nasal Mucosa/immunology ; Reactive Oxygen Species/metabolism ; Respiratory Mucosa/immunology ; Rhinitis/immunology ; Sinusitis/immunology ; Up-Regulation ; Young Adult
Abstract
High-mobility group box 1 (HMGB1) mediates various functions according to the location. We tried to investigate the role of HMGB1 in upper airway under hypoxic conditions. We cultured primary normal human nasal epithelium (NHNE) cells under hypoxic conditions and evaluated the movement of HMGB1 by western blotting, immunofluorescence, and enzyme-linked immunosorbent assay (ELISA). Reactive oxygen species (ROS) level was evaluated to estimate the translocation mechanism of HMGB1. The role of secreted HMGB1 was evaluated by ELISA assay. Furthermore, we collected human nasal mucosa samples and nasal lavage fluids from patients conditioned under hypoxic and non-hypoxic environment, and compared the expression of HMGB1 in human nasal mucosa samples by immunohistochemistry and the levels of HMGB1 in lavage fluids using ELISA assay. Hypoxia induced translocation of HMGB1 into the extracellular area and it was dependent on ROS produced by dual oxidase 2. Secreted HMGB1 was involved in the upregulation of interleukin (IL)-8. In human samples, HMGB1 was translocated from nucleus to the cytoplasm in hypoxic-conditioned nasal mucosa. HMGB1 was increased in nasal lavage samples of chronic rhinosinusitis patients, whose sinus mucosa was supposed to be hypoxic as compared with controls. We suggest that HMGB1 is secreted in hypoxic condition via ROS-dependent mechanism and secreted HMGB1 participates in IL-8 upregulation mediating inflammatory response.
Full Text
http://www.nature.com/articles/mi201682
DOI
10.1038/mi.2016.82
Appears in Collections:
1. College of Medicine (의과대학) > Dept. of Otorhinolaryngology (이비인후과학교실) > 1. Journal Papers
Yonsei Authors
Kim, Kyung Su(김경수) ORCID logo https://orcid.org/0000-0003-1460-0640
Kim, Chang Hoon(김창훈) ORCID logo https://orcid.org/0000-0003-1238-6396
Yoon, Joo Heon(윤주헌)
URI
https://ir.ymlib.yonsei.ac.kr/handle/22282913/160669
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