Urban Particulate Matters May Affect Endoplasmic Reticulum Stress and Tight Junction Disruption in Nasal Epithelial Cells

Am J Rhinol Allergy. 2021 Nov;35(6):817-829. doi: 10.1177/19458924211004006. Epub 2021 Mar 18.

Abstract

Background: Exposure to airborne urban particulate matter (UPM) has been closely related to the development and aggravation of respiratory disease, including sinonasal disorders.

Objective: The aims of this study were to investigate the effect of UPM on nasal epithelial tight junctions (TJs) and mucosal barrier function and delineate the underlying mechanism by using both in vitro and in vivo models.

Methods: In this study, human nasal epithelial cells (hNECs) and BALB/c mice were exposed to UPMs. UPM 1648a and 1649 b were employed. TJ and endoplasmic reticulum (ER) stress marker expression was measured using western blot analysis and immunofluorescence. TJ integrity and nasal epithelial barrier function were evaluated by transepithelial electric resistance (TER) and paracellular flux. In addition, the effects of N-acetyl-L-cysteine (NAC) on UPM-induced nasal epithelial cells were investigated.

Results: UPM significantly impaired the nasal epithelial barrier, as demonstrated by decreased protein expression of TJ and ER stress markers in human nasal epithelial cells. This finding was in parallel to reduced transepithelial electrical resistance and increased fluorescein isothiocyanate-dextran permeability. Pretreatment with NAC decreased the degree of UPM-mediated ER stress and restored nasal epithelial barrier disruption in human nasal epithelial cells (hNEC) and the nasal mucosa of experimental animals.

Conclusion: These data suggest that UPMs may induce nasal epithelial barrier dysfunction by targeting TJs and ER stress could be related in this process. Based on these results, we suggest that suppression of this process with an inhibitor targeting ER stress responses could represent a novel promising therapeutic target in UPM-induced sinonasal disease.

Keywords: endoplasmic reticulum; epithelial cells; paranasal sinus disease; particulate matter; tight junction.

MeSH terms

  • Animals
  • Endoplasmic Reticulum Stress
  • Epithelial Cells
  • Mice
  • Mice, Inbred BALB C
  • Particulate Matter* / toxicity
  • Tight Junctions*

Substances

  • Particulate Matter