Science review:: Redox and oxygen-sensitive transcription factors in the regulation of oxidant-mediated lung injury:: role for nuclear factor-κB

The primary role of pulmonary airways is to conduct air to the alveolar epithelium, where gas exchange can efficiently occur. Injuries to airways resulting from inhalation of airborne pollutants and parenteral exposure to ingested pollutants that cause oxidative stress have the potential to interfere with this process. A progressive rise of oxidative stress due to altered reduction-oxidation (redox) homeostasis appears to be one of the hallmarks of the processes that regulate gene transcription in lung physiology and pathophysiology. Reactive metabolites serve as signaling messengers for the evolution and perpetuation of the inflammatory process that is often associated with cell death and degeneration. Redox-sensitive transcription factors are often associated with the development and progression of many human disease states and inflammatory-related injury, particularly of the lung. The present review elaborates on the role of the redox-sensitive and oxygen-sensitive transcription factor NF-kappaB in mediating lung injury. Changes in the pattern of gene expression through regulatory transcription factors are crucial components of the machinery that determines cellular responses to oxidative and redox perturbations. Additionally, the discussion of the possible therapeutic approaches of antioxidants, thiol-related compounds and phosphodiesterase inhibitors as anti-inflammatory agents will thereby help understand the oxidant/redox-mediated lung injury mechanisms.