HMGB1 increases IL-8 secretion under hypoxic condition in human nasal epithelia (INC1P.358)

Abstract

Abstract Objectives High Mobility Group Box 1 (HMGB1) is a nuclear protein. It has been found that HMGB1 can be secreted into extracellular area via various mechanisms, and extracellular HMGB1 have a potential to mediate proinflammatory signaling. The aim of the present study was to investigate the role of HMGB1 in upper airway epithelial cells under hypoxic condition. Materials and Methods We cultured normal human nasal epithelial cells (NHNE). Cells were incubated in hypoxic condition and evaluated whether HMGB1 was secreted into extracellular area. Next, we harvested human nasal mucosa samples and nasal lavage fluids which were supposed to be hypoxic and non-hypoxic condition. We compared the expression of HMGB1 in human nasal mucosa samples by immunohistochemistry and the amount of HMGB1 in lavage fluids using ELISA assay. Results We found that hypoxia induced translocation of HMGB1 into extracellular area in NHNE cells and it was ROS dependent. We identified that secreted HMGB1 protein was participating in up-regulation of IL-8. In addition, much more cytoplasmic HMGB1 was identified in hypoxic conditioned human sino-nasal mucosa compared to control. The amount of HMGB1 in nasal lavage fluids was also increased in hypoxic conditioned patients compared to control Conlcusion: These findings suggest that HMGB1 plays a role in the pathogenesis of hypoxia-mediated inflammation in upper airway epithelium.