Hypoxia Increases Epithelial Permeability in Human Nasal Epithelia

Abstract

Objectives:

The nasal mucosa is the first site that encounters pathogens and forms continuous barriers to various stimuli. Here, we studied the effect of hypoxia on barrier function in normal human nasal epithelial (NHNE) cells. The expression levels of various junction complex proteins were assessed in hypoxia-stimulated NHNE cells and human nasal mucosal tissues.

Methods:

We performed real-time polymerase chain reaction analysis, western blotting, and immunofluorescence assays to examine differences in the mRNA and protein expression of ZO-1 and E-cadherin in NHNE cells. Moreover, we evaluated the transepithelial resistance (TER) of NHNE cells after hypoxic stimuli to check for changes in permeability. The expression of ZO-1 and E-cadherin was measured in human nasal mucosa samples by western blotting.

Results:

Hypoxia time-dependently decreased the expression of ZO-1 and E-cadherin at the gene and protein levels. We also found that hypoxia decreased the TER of NHNE cells, which indicated increased permeability. Human nasal mucosa samples, which are supposed to be hypoxic, showed significantly decreased levels of ZO-1 and E-cadherin expression compared to control.

Conclusions:

Our results demonstrate that hypoxic condition in the nasal cavity, which can occur because of natural ostium obstruction, alters the expression of junction complex molecules and increases epithelial permeability in human nasal epithelia. This suggests that hypoxia is a major pathogenic mechanism of rhinosinusitis through its effect of deteriorating barrier function.