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

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.

Decoding chronic rhinosinusitis: A metabolomics‐based approach

“…Increased metabolism in CRS patients could lead to ROS accumulation, 40 cause the continuous inflammation, and further contribute to pathophysiological dysfunction. 41 Additionally, Another study supported the notion that mitochondrial dysfunction might play a role in the pathogenesis of CRSwNP, 42 impaired mitochondria could activate the inflammatory pathway, consequently increasing the release of cytokines. Arginine, a wellknown substrate for nitric oxide (NO) production, has been linked to cellular metabolism, inflammation, and immune responses.…”

Proteomics and metabolomics analysis of nasal lavage fluid in chronic rhinosinusitis with nasal polyps

“…In addition, damaged mitochondria may activate the inflammasome pathway, resulting in increased cytokine release. Another study reported that mitochondrial dysfunction may be associated with the pathogenesis of CRSwNP 15 …”

“…Another study reported that mitochondrial dysfunction may be associated with the pathogenesis of CRSwNP. 15 To the best of our knowledge, this is the first integrated multi-omic analysis combining both proteomic and metabolomic data of CRSwNP patients. Key proteins and metabolites involved in mitochondrial function and metabolism of arginine and alpha-linolenic acid may be new therapeutic targets for CRSwNP.…”

Povidone iodine suppresses LPS-induced inflammation by inhibiting TLR4/MyD88 formation in airway epithelial cells

“…The signal produced is proportional to the amount of analyte bound. The bands' intensities were analyzed using Quick Spots Image Analysis Software (Western Vision Software, http://www.wvision.com/QuickSpots.html ) 33 .…”