Our lungs are exposed daily to airborne
pollutants,
particulate matter, pathogens as well as lung
allergens and irritants. Exposure to these substances can lead to inflammatory responses and may induce endogenous
oxidant production, which can cause chronic
inflammation, tissue damage and remodeling. Notably, the development of
asthma and
Chronic Obstructive Pulmonary Disease (
COPD) is linked to the aforementioned irritants. Some inhaled foreign chemical compounds are rapidly absorbed and processed by phase I and II
enzyme systems critical in the detoxification of
xenobiotics including the
glutathione-conjugating
enzymes Glutathione S-
transferases (
GSTs).
GSTs, and in particular genetic variants of
GSTs that alter their activities, have been found to be implicated in the susceptibility to and progression of these
lung diseases. Beyond their roles in phase II metabolism, evidence suggests that
GSTs are also important mediators of normal lung growth. Therefore, the contribution of
GSTs to the development of
lung diseases in adults may already start in utero, and continues through infancy, childhood, and adult life.
GSTs are also known to scavenge
oxidants and affect signaling pathways by
protein-
protein interaction. Moreover,
GSTs regulate reversible oxidative post-translational modifications of
proteins, known as
protein S-glutathionylation. Therefore,
GSTs display an array of functions that impact the pathogenesis of
asthma and
COPD. In this review we will provide an overview of the specific functions of each class of mammalian cytosolic
GSTs. This is followed by a comprehensive analysis of their expression profiles in the lung in healthy subjects, as well as alterations that have been described in (epithelial cells of) asthmatics and
COPD patients. Particular emphasis is placed on the emerging evidence of the regulatory properties of
GSTs beyond detoxification and their contribution to (un)healthy lungs throughout life. By providing a more thorough understanding, tailored therapeutic strategies can be designed to affect specific functions of particular
GSTs.