Young HY, Sun HE, et al. Altered Mitochondrial Functions and Morphologies in Epithelial Cells Are Associated With Pathogenesis of Chronic Rhinosinusitis With Nasal Polyps. Allergy Asthma Immunol Res. 2020 Jul;12(4):653-668
Chronic rhinosinusitis with nasal polyps (CRSwNP) is a complex inflammatory disease of the nasal and paranasal sinus mucosa . There are indications that the disease is associated with mitochondrial dysfunction, structural changes in the mitochondria, and reactive oxygen species (ROS) generation [2-5]. Staphylococcus aureus enterotoxin B (SEB) is found in the nasal cavity and polyp tissues of CRSwNP patients and can induce the production of reactive oxygen species (ROS) and endoplasmic reticulum (ER) stress in epithelial cells in CRSwNP [6,7]. This study investigated whether there are functional and morphological changes in the mitochondria in the epithelial cells of nasal polyps (NPs) and SEB-stimulated nasal epithelial cells.
Figure. Quantitative expression derived from relative optical density analyses of western blots (normalised signal/beta actin expression). Oxidative phosphorylation complex (COX) I–V expression levels in nasal polyp (NP) tissue (control, n = 4; UT, n = 8; NP, n = 8). UT, uncinate tissue; NP, nasal polyp. *P < 0.05; †P < 0.01; ‡P < 0.005.
Participants were 30 patients with CRSwNP and 15 healthy subjects. It should be noted that CRSwNP subjects were not specifically classified as eosinophilic, and neutrophilic CRSwNP has been observed in some Asian subjects. 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.
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 (see Figure).
Generation of mtROS was increased following SEB exposure in nasal epithelial cells and was reduced by pretreatment with MitoTEMPO, an mtROS scavenger. mtROS was increased in the NPs of CRSwNP patients compared to the UT of controls or CRSwNP patients. These results indicated that an increase in mtROS might be the source of the oxidative stress that affects the pathophysiology of NPs .
Mitochondrial structures were dysregulated following SEB stimulation in human nasal epithelial cells and NPs. These findings indicated that the dynamics of mitochondria in CRSwNP increased due to oxidative stress.
This study demonstrates that functional and structural changes in mitochondria, including mtROS generation, bioenergetics changes, and morphological changes can be induced by SEB exposure in vitro and in the polyp tissues of CRSwNP patients. These findings indicate that such changes may be associated with the pathogenesis of CRSwNP, and future research is needed to validate the therapeutic potential of mitochondria-specific antioxidants targeting mtROS in relevant disease models.
- Kim DW, Cho SH. Emerging endotypes of chronic rhinosinusitis and its application to precision medicine. Allergy Asthma Immunol Res 2017;9:299-306.
- Yoo SM, Jung YK. A molecular approach to mitophagy and mitochondrial dynamics. Mol Cells 2018;41:18-26.
- Aguilera-Aguirre L, Bacsi A, Saavedra-Molina A, Kurosky A, Sur S, Boldogh I. Mitochondrial dysfunction increases allergic airway inflammation. J Immunol 2009;183:5379-87.
- Kim SR, Kim DI, Kim SH, Lee H, Lee KS, Cho SH, et al. NLRP3 inflammasome activation by mitochondrial ROS in bronchial epithelial cells is required for allergic inflammation. Cell Death Dis 2014;5:e1498.
- Kaminski MM, Sauer SW, Klemke CD, Süss D, Okun JG, Krammer PH, et al. Mitochondrial reactive oxygen species control T cell activation by regulating IL-2 and IL-4 expression: mechanism of ciprofloxacin-mediated immunosuppression. J Immunol 2010;184:4827-4
- Kim DW, Eun KM, Jin HR, Cho SH, Kim DK. Prolonged allergen exposure is associated with increased thymic stromal lymphopoietin expression and Th2-skewing in mouse models of chronic rhinosinusitis. Laryngoscope 2016;126:E265-72.
- Kim YM, Jin J, Choi JA, Cho SN, Lim YJ, Lee JH, et al. Staphylococcus aureus enterotoxin B-induced endoplasmic reticulum stress response is associated with chronic rhinosinusitis with nasal polyposis. Clin Biochem 2014;47:96-103.
- Cloonan SM, Choi AM. Mitochondria in lung disease. J Clin Invest 2016;126:809-20.