Source: International Congress 2014 – Cell biology 2014
Disease area: Airway diseases

Abstract

Introduction Recent studies proved mitochondrial DNA fragments (mtDNA) were released to the extracellular space and closely involved in modulating native immune response. However, the role of extracellular mtDNA in pathogenesis of COPD is unclearObjective We measured circulating mtDNA level and pro-inflammatory factors in COPD patients and investigate the role of its specific receptor toll-like receptor 9 (TLR9)Methods 122 COPD patients and 79 controls were recruited. mtDNA copies(specific mitochondrial gene ND1,CYTB,COXIII)in patients serum and supernatants of airway epithelium cells were determined using qRT-PCR.TNF-a,IL-8,CRPwere assayed by multiplexing ELISA. Further investigation on TLR9 in CSE induced cell signaling activation was performed at RNA and protein level using antagonist.Results In COPD patients, serum mtDNA increased significantly with increasing severity. mtDNA level in smokers was 1.3 fold higher compared to non-smokers(ND1copies 5.9±1.3x10^4Vs4.6±1.1x10^4,p<0.05).There is an elevation of IL-8 level in patients compared to controls(4.86±2.26Vs6.14±3.12ng/ml,p<0.05). Correlation analysis showed serum mtDNA COXIII was positively correlated with IL-8 (r=0.375,p=0.033).Abundant mtDNA was found to release extracellularly from 16HBE and H292 when induced by CSE. The expression of TLR9 significantly increased in a dose and time-dependent manner and blockage of TLR9 inhibited CSE induced MAPK signaling pathway activationConclusions:Elevation of circulating mtDNA level is found prevalent in patients with increasing COPD severity and positively correlated with IL-8. Extracellular mtDNA may play an essential role in modulating airway inflammation in COPD.

Rating:

Share or cite this content

Citations should be made in the following way:
X. Li, T. Wang, Y. Shen, D. Xu, L. Liu, F. Wen (Chengdu, China). The role of circulating mitochondrial DNA in modulating airway inflammation of chronic obstructive pulmonary disease. Eur Respir J 2014; 44: Suppl. 58, 3858

Member's Comments

No comment yet.

Related content which might interest you: Comparison of inflammatory markers in induced and spontaneous sputum in COPD patients Source: International Congress 2014 – Translational studies in COPD Year: 2014 Inflammatory cell microlocalisation and airway dysfunction: cause and effect? Source: Eur Respir J 2007; 30: 1043-1056 Year: 2007 Differential bronchoalveolar expression of candidate microRNAs in chronic obstructive pulmonary disease, asthma bronchiale and pulmonary sarcoidosis Source: International Congress 2014 – Novel epigenetic regulators for targeting via nanomedicine Year: 2014 Modulation of inflammation by benralizumab in eosinophilic airway disease Source: International Congress 2016 – Novel mechanisms and treatment modalities in asthma Year: 2016 Role of CD69 in the pathogenesis of elastase-induced pulmonary inflammation and emphysema Source: International Congress 2016 – New findings in mucosal immunology Year: 2016 Disturbed pulmonary immunity and the phenotype of alveolar macrophages in bronchial asthma, gastroesophageal reflux disease and their combination Source: International Congress 2014 – New insights into monocyte and macrophage biology Year: 2014 Interleukin-18 levels in induced sputum of stable and exacerbated COPD patients Source: International Congress 2014 – Translational studies in COPD Year: 2014 Tiotropium effects on airway inflammatory events in the cat as an animal model for acute cigarette smoke-induced lung inflammation Source: International Congress 2014 – Animal models: asthma, COPD and beyond Year: 2014 Role of IL-33/ST2 axis in systemic inflammation of allergic airway disease Source: International Congress 2014 – New mechanisms in the pathogenesis of asthma and other lung diseases Year: 2014 Survivin in patients with chronic obstructive pulmonary disease Source: International Congress 2015 – Monitoring and phenotyping COPD Year: 2015 Dynamics of sputum antimicrobial peptide levels in chronic obstructive pulmonary disease (COPD) Source: International Congress 2015 – Infection in COPD: different aspects of the host/pathogen balance Year: 2015 Common airway variants and chronic obstructive pulmonary disease Source: International Congress 2015 – New observations in respiratory epidemiology Year: 2015 The novel compound Sul-121 inhibits inflammation in experimental models of chronic obstructive pulmonary disease Source: International Congress 2016 – New signalling pathways in COPD Year: 2016 Oxidative stress and systemic inflammation in different COPD phenotypes Source: International Congress 2014 – Monitoring COPD with different biomarkers Year: 2014 Smoking alters alpha1-antitrypsin in alveolar macrophages possibly promoting misfolding Source: International Congress 2014 – New studies into pulmonary proteases and antiproteases Year: 2014 Adiponectin is associated with dynamic hyperinflation and a favourable response to inhaled glucocorticoids in patients with COPD Source: International Congress 2014 – Translational studies in COPD Year: 2014 Increased serum level of apelin in chronic obstructive pulmonary disease Source: International Congress 2015 – COPD: interesting notes Year: 2015 Dysregulation of serum miRNA in chronic obstructive pulmonary disease Source: International Congress 2015 – Genetics, genomics and exposures in asthma and COPD Year: 2015 Pulmonary senescence in chronic obstructive pulmonary disease is primarily mediated by persistent DNA double strand breaks Source: Annual Congress 2013 –Tobacco use in different countries: crisis to disease Year: 2013 The role of chemokine receptors in the aberrant migration of COPD neutrophils Source: International Congress 2014 – Cell biology 2014 Year: 2014