PT  - JOURNAL ARTICLE
AU  - Charalambos Michaeloudes
AU  - Coen Wiegman
AU  - Paul Kirkham
AU  - Kian Fan Chung
AU  - Ian Adcock
AU  - COPD MAP Consortium WP3
TI  - Mitochondrial reactive oxygen species (ROS) mediate proliferation and cytokine release in airway smooth muscle cells of patients with COPD
DP  - 2014 Sep 01
TA  - European Respiratory Journal
PG  - P3845
VI  - 44
IP  - Suppl 58
4099  - http://erj.ersjournals.com/content/44/Suppl_58/P3845.short
4100  - http://erj.ersjournals.com/content/44/Suppl_58/P3845.full
SO  - Eur Respir J2014 Sep 01; 44
AB  - Background: The inflammatory response in COPD is accompanied by small airway remodelling, with increased airway smooth muscle (ASM) mass, as a result of ASM cell (ASMC) hyperplasia. Oxidative stress, a key mediator of inflammation and remodelling in COPD, triggers mitochondrial dysfunction and increased ROS levels in ASMCs from healthy subjects. Mitochondrial ROS release is more pronounced in ASMCs from patients with COPD suggesting an inherent mitochondrial dysfunction. We hypothesised that mitochondrial ROS may trigger the hyperproliferative ASMC phenotype observed in COPD. Aims and Objectives: The role of mitochondrial ROS in mediating proliferation and inflammatory mediator release from ASMCs of patients with COPD was investigated. Methods: ASMCs were isolated from bronchoscopic biopsies of healthy non-smokers and patients with COPD. Cell proliferation was measured as rate of BrdU incorporation and total cellular DNA. The role of mitochondrial ROS was studied using the mitochondria-targeted antioxidant MitoQ (1µM) and the mitochondria-permeable antioxidant Tiron (0.1-10mM). Results: Foetal bovine serum (FBS; 2.5%) and TGF-β (1ng/mL) increased the proliferation of ASMCs from healthy subjects (∼30-fold; p<0.001) and patients with COPD (∼40-fold; p<0.001). FBS and TGF-β-induced proliferation of ASMCs, from both groups, was reduced by pre-treatment with MitoQ (∼50%; p<0.05) or Tiron (∼80%; p<0.01). MitoQ also partially inhibited TNF-α (0.1ng/ml)-induced IL-8 release in ASMCs from both groups. Conclusion: Mitochondrial oxidative stress may be an interesting target for preventing ASMC hyperproliferation in COPD.