Allergy Asthma Immunol Res.  2020 Jul;12(4):653-668. 10.4168/aair.2020.12.4.653.

Altered Mitochondrial Functions and Morphologies in Epithelial Cells Are Associated With Pathogenesis of Chronic Rhinosinusitis With Nasal Polyps

Affiliations
  • 1Department of Otorhinolaryngology-Head and Neck Surgery, Research Institute for Medical Sciences, Chungnam National University School of Medicine, Daejeon, Korea
  • 2Department of Medical Science, Chungnam National University School of Medicine, Daejeon, Korea
  • 3Department of Biochemistry, Research Institute for Neurosciences, Chungnam National University School of Medicine, Daejeon, Korea
  • 4Korea Research Institute of Bioscience and Biotechnology, Daejeon, Korea
  • 5State Key Laboratory of Respiratory Disease, Department of Otorhinolaryngology-Head and Neck Surgery, First Affiliated Hospital, Guangzhou Medical University, Guanzhou, China

Abstract

Purpose
Chronic rhinosinusitis with nasal polyps (CRSwNP) is a complex inflammatory disease of the nasal and paranasal sinus mucosa. The disease is associated with mitochondrial dysfunction, structural changes in the mitochondria, and reactive oxygen species (ROS) generation. This study investigated whether there are functional and morphological changes in the mitochondria in the epithelial cells of nasal polyps (NPs) and Staphylococcus aureus enterotoxin B (SEB)-stimulated nasal epithelial cells.
Methods
In all, 30 patients with CRSwNP and 15 healthy subjects were enrolled. Mitochondrial ROS (mtROS) and changes in mitochondrial functions and structures were investigated in the uncinate tissue (UT) of healthy controls, the UT or NPs of CRSwNP patients, and human nasal epithelial cells with or without SEB stimulation.
Results
Oxidative phosphorylation complexes showed various responses following SEB stimulation in the nasal epithelial cells, and their expressions were significantly higher in the NPs of patients with CRSwNP than in the UT of controls. Generation of mtROS was increased following SEB exposure in nasal epithelial cells and was reduced by pretreatment with MitoTEMPO, which is used as an mtROS scavenger. In the tissues, mtROS was significantly increased in the NPs of CRSwNP patients compared to the UT of controls or CRSwNP patients. The expressions of fusion- and fission-related molecules were also significantly higher in SEB-exposed nasal epithelial cells than in non-exposed cells. In tissues, the expression of fission (fission mediator protein 1)- and fusion (membrane and mitofusin-1, and optic atrophy protein 1)-related molecules was significantly higher in the NPs of CRSwNP patients than in UT of controls or CRSwNP patients. Transmission electron microscopy revealed elongated mitochondria in SEB-exposed nasal epithelial cells and epithelial cells of NPs.
Conclusions
Production of mtROS, disrupted mitochondrial function, and structural changes in nasal epithelial cells might be involved in the pathogenesis of CRSwNP.

Keyword

Rhinitis; mitochondria; reactive oxygen species; nasal polyps; Staphylococcus; enterotoxin; epithelial cells
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