Molecular mechanisms of oxidative stress in airways and lungs with reference to asthma and chronic obstructive pulmonary disease

Abstract

Oxidative stress is an important pathophysiological component of airway diseases such as asthma and chronic obstructive pulmonary disease (COPD), which cause significant morbidity and mortality. Oxidative stress leads to the activation of transcription factors and signaling pathways, partly through the activation of the innate immune response through toll-like receptors 2 and 4. Such activation leads to the release of cytokines and chemokines. In addition, adaptive immune responses are initiated through activation of dendritic cells and antigen presentation to T-helper cells, with direct activation of NKT cells. Corticosteroid insensitivity is a feature of severe asthma and COPD, and oxidative stress is an important factor in its development by inhibition of HDAC-2 activity and expression through serine hyperphosphorylation. Activation of kinases such as p38 mitogen-activated protein kinase or phospho-inositol 3-kinase delta may also be involved through phosphorylation of the glucocorticoid receptor. Antioxidants may prove to be beneficial in inhibiting inflammatory responses and restoring corticosteroid function.