Mitochondrial fusion is induced by mitochondrial ROS in Aspergillus fumigatus-induced severe eosinophilic asthma

Author:

Kim, SR1; Lee, YC1; Park, HJ1; Kim, DI1; Kim, SH2

Author address:

1 Chonbuk National University Medical School, Jeonju, Korea; 2 LG Life Sciences Ltd., Seoul, Korea

Full conference title:

European Academy of Allergy and Clinical Immunology Congress 2015

Date: 5 August 2020

Abstract:

Background: Mitochondria are dynamic organelles that undergo fission and fusion events, but we are only beginning to understand some of the reasons and the machineries involved in these processes. Recent studies have demonstrated that under persistent stressful condition, that is, pathologic condition, the balance between fission and fusion of mitochondria is out of control. However, there is little information on mitochondrial dynamics in the pathogenesis of bronchial asthma, especially fungus-induced allergic airway inflammation.

Method: In this study, we aimed to evaluate the morphologic changes of mitochondria in airway inflammatory cells from a murine model of bronchial asthma.

Results: The mice sensitized and challenged with Aspergillus fumigatus (Af-inhaled mice) showed the typical features of bronchial asthma; increased airway inflammatory cells, the pathologic changes, the increased levels of Th2 cytokines in lungs of Af-inhaled mice, and increased bronchial hyper-responsiveness. Interestingly, these asthmatic features were refractory to the treatment with oral dexamethasone, whereas they were improved significantly by the administration of mitochondrial ROS inhibitor, NecroX-7. In addition, electron-microscopic analysis revealed that in BAL cells from Af-inhaled mice, the mitochondria were dramatically elongated, fused each other compared to the finding of cells from control mice. The levels of MFN1 and MFN2, mitochondrial fusion proteins, were significantly increased in lung tissues of Af-inhaled mice. Consistent with the results on the asthmatic features in the treatment with dexamethasone or NecroX-7, administration of dexamethasone, a current representative therapeutic agent for bronchial asthma, did not affect the increases in MFN1 and MFN2 levels and morphological changes, but NecroX-7 decreased the expression of MFN1 and MFN2 and restored the morphology of mitochondria.

Conclusion: These findings indicate that the mitochondrial hyper-fusion may be induced by fungal allergen stimulation in airway inflammatory cells and it can be one of the molecular mechanisms for the pathogenesis of steroid-resistant allergic airway inflammation.

Abstract Number: 195

Link to conference website:

Link Conference abstract: 

EAACI 2015

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