The Role of Nf-Kappa and HDCA and Implication of Oxidative Stress in Airway Inflammation of Chronic Obstructive Pulmonary Disease

Abstract

Oxidative stress has been implicated in the pathogenesis of Chronic Obstructive Pulmonary Disease (COPD), due to its effect on proinflammatory gene transcription. Oxidants/antioxidants imbalance is responsible for disease development. The study was designed to assess oxidative stress and inflammation in COPD patients. The level of TNF-α and IL-8 in sputum and BAL were compared. NF-κB and HDAC were measured in BAL leucocytes. Oxidative stress was evaluated by assessment of MDA levels in BAL and antioxidant markers: TAS, GSH, GSH-Px activity, vitamin E and vitamin C in BAL and uric acid in serum. Design and Methods. Sixty patients with COPD were recruited from Medical Biochemistry Department, in collaboration with the Chest hospital, Ain Shams University and compared to 20 control (smokers and nonsmokers) subjects. The patients were divided to three groups (GOLD stage II, III and IV) according to the severity of disease. Results. Concentrations of TNF-α and IL-8 were significantly elevated in both sputum and BAL compared to controls. MDA level increased while antioxidants (TAS, GSH, GSH-Px, vitamin E, vitamin C and uric acid) decreased in patients compared to the controls. Oxidants stress also alters the activity of HDAC and NF-κB. There was a significant negative correlation between MDA and all antioxidant markers (p<0.000), also HDAC and NF-κB (p<0.000). Conclusion. There is evidence of increased oxidative stress in the airways of patients with COPD. Understanding the mechanisms of TNF-α inhibition, NF-κB regulation, histone acetylation/deacetylation balance may support the development of novel therapies that limit lung inflammation and injury.