title: Mitochondrial structural changes and dysfunction are associated with experimental allergic asthma.
abstract: An imbalance between Th1 and Th2 immune response is crucial for the development of pathophysiological features of asthma. A Th2-dominant response produces oxidative stress in the airways, and it is thought to be one of the crucial components of asthma pathogenesis. Although mitochondrion is a crucial organelle to produce endogenous reactive oxygen species, its involvement in this process remains unexplored as yet. We demonstrate in this study that OVA-induced experimental allergic asthma in BALB/c mice is associated with mitochondrial dysfunction, such as reduction of cytochrome c oxidase activity in lung mitochondria, reduction in the expression of subunit III of cytochrome c oxidase in bronchial epithelium, appearance of cytochrome c in the lung cytosol, decreased lung ATP levels, reduction in the expression of 17 kDa of complex I in bronchial epithelium, and mitochondrial ultrastructural changes such as loss of cristae and swelling. However, there was no change in the expression of subunits II and III of cytochrome c oxidase. Interestingly, administration of IL-4 mAb reversed these mitochondrial dysfunction and structural changes. In contrast, IFN-gamma mAb administration neither reversed nor further deteriorated the mitochondrial dysfunction and structural changes compared with control asthmatic mice administered with isotypic control Ab, although airway hyperresponsiveness deteriorated further. These results suggest that mitochondrial structural changes and dysfunction are associated with allergic asthma. These findings may help in the development of novel drug molecules targeting mitochondria for the treatment of asthma.
authors: Molecular Immunogenetics Laboratory, Institute of Genomics and Integrative Biology, Delhi, India.
authors: Ulaganathan
authors: U
authors: Mabalirajan
authors: Amit Kumar
authors: AK
authors: Dinda
authors: Sarvesh
authors: S
authors: Kumar
authors: Reema
authors: R
authors: Roshan
authors: Pooja
authors: P
authors: Gupta
authors: Surendra Kumar
authors: SK
authors: Sharma
authors: Balaram
authors: B
authors: Ghosh
mesh_terms: D000818:Animals; D000911:Antibodies, Monoclonal / Q000494:pharmacology; D001249:Asthma / Q000473:pathology*; D004195:Disease Models, Animal; D007371:Interferon-gamma / Q000276:immunology; D015847:Interleukin-4 / Q000276:immunology; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D008928:Mitochondria / Q000737:chemistry / Q000473:pathology* / Q000648:ultrastructure; D024101:Mitochondrial Proteins / Q000378:metabolism; D012137:Respiratory System
chemical_list: D000911:Antibodies, Monoclonal; D024101:Mitochondrial Proteins; D015847:Interleukin-4; D007371:Interferon-gamma