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

Area of Science:

• Cell Biology
• Immunology
• Otorhinolaryngology

Background:

• High-mobility group box 1 (HMGB1) protein exhibits diverse functions contingent on its cellular localization.
• Understanding HMGB1's role in the upper airway under hypoxic stress is crucial for respiratory health.

Purpose of the Study:

• To investigate the function of HMGB1 in normal human nasal epithelium (NHNE) cells under hypoxic conditions.
• To elucidate the mechanism of HMGB1 translocation and its involvement in inflammatory responses within the upper airway.

Main Methods:

• Primary NHNE cells were cultured under hypoxia and analyzed for HMGB1 translocation using western blotting, immunofluorescence, and ELISA.
• Reactive oxygen species (ROS) levels and dual oxidase 2 activity were assessed to determine the HMGB1 translocation mechanism.
• Human nasal mucosa and lavage fluid samples from hypoxic and non-hypoxic individuals were analyzed via immunohistochemistry and ELISA.

Main Results:

• Hypoxia induced HMGB1 translocation to the extracellular space in NHNE cells, a process dependent on ROS generated by dual oxidase 2.
• Secreted HMGB1 was found to upregulate interleukin-8 (IL-8) production.
• In human samples, hypoxic nasal mucosa showed HMGB1 translocation from the nucleus to the cytoplasm.
• Elevated HMGB1 levels were observed in nasal lavage fluids of chronic rhinosinusitis patients, suggesting a link to hypoxic sinus mucosa.

Conclusions:

• HMGB1 is secreted from nasal cells under hypoxic conditions through a ROS-dependent pathway.
• Secreted HMGB1 contributes to the inflammatory response by mediating IL-8 upregulation.
• HMGB1 translocation and secretion represent a significant mechanism in hypoxic upper airway inflammation.