ROS-dependent HMGB1 secretion upregulates IL-8 in upper airway epithelial cells under hypoxic condition.
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.
Department of Otorhinolaryngology-Head and Neck Surgery, Chung-Ang University College of Medicine, Seoul, Republic of Korea.
H J
HJ
Min
The Research Center for Human Natural Defense System, Yonsei University College of Medicine, Seoul, Republic of Korea.
J-H
JH
Kim
The Research Center for Human Natural Defense System, Yonsei University College of Medicine, Seoul, Republic of Korea.|The Airway Mucus Institute, Yonsei University College of Medicine, Seoul, Republic of Korea.
J E
JE
Yoo
Brain Korea 21 PLUS Project for Medical Science, Yonsei University College of Medicine, Seoul, Republic of Korea.
J-H
JH
Oh
Department of Otorhinolaryngology-Head and Neck Surgery, Chung-Ang University College of Medicine, Seoul, Republic of Korea.
K S
KS
Kim
The Research Center for Human Natural Defense System, Yonsei University College of Medicine, Seoul, Republic of Korea.|The Airway Mucus Institute, Yonsei University College of Medicine, Seoul, Republic of Korea.|Department of Otorhinolaryngology, Yonsei University College of Medicine, Seoul, Republic of Korea.
J-H
JH
Yoon
The Airway Mucus Institute, Yonsei University College of Medicine, Seoul, Republic of Korea.|Department of Otorhinolaryngology, Yonsei University College of Medicine, Seoul, Republic of Korea.
C-H
CH
Kim
D000328:Adult; D002478:Cells, Cultured; D002908:Chronic Disease; D000074623:Dual Oxidases / Q000378:metabolism; D005260:Female; D024243:HMGB1 Protein / Q000378:metabolism*; D006801:Humans; D000860:Hypoxia / Q000276:immunology*; D016209:Interleukin-8 / Q000235:genetics / Q000378:metabolism*; D008297:Male; D008875:Middle Aged; D009297:Nasal Mucosa / Q000276:immunology*; D017382:Reactive Oxygen Species / Q000378:metabolism*; D020545:Respiratory Mucosa / Q000276:immunology*; D012220:Rhinitis / Q000276:immunology*; D012852:Sinusitis / Q000276:immunology*; D015854:Up-Regulation; D055815:Young Adult
D024243:HMGB1 Protein; C585491:HMGB1 protein, human; D016209:Interleukin-8; D017382:Reactive Oxygen Species; D000074623:Dual Oxidases