with correction of this imbalanced redox state (Garcia-Ruiz et al., 1995;Zhou et al., 2005). Antioxidant defenses, of which Cys and GSH are just two components, are vital for cellular protection against oxidative stress. When faced with such stresses, cells respond by activating the antioxidant response element (ARE), a genetic program that is regulated by its major transcription factor, nuclear factor erythroid 2–related factor 2 (Nrf2). The ARE/Nrf2 pathway thereby serves as a broad-based defense system against diverse oxidative stresses. Importantly, several studies suggest that it plays an important role in counteracting the oxidative stress created by chronic alcohol use (Kim et al., 2009;Dong et al., 2008;Cederbaum, 2006). However, we have shown that chronic alcohol ingestion causes profound oxidative stress within the lower airways of experimental animals and in otherwise healthy human subjects (Holguin et al., 1998;Moss et al., 2000). The mechanisms responsible for alcohol-induced oxidative stress are poorly understood, and the failure to mount an appropriate anti-oxidant response within the alveolar space suggests that chronic alcohol ingestion may interfere with the ARE/Nrf2 pathway in this unique microenvironment.
