Abstract
Much of what is known about the Aryl Hydrocarbon Receptor (AhR) centers on its ability to mediate the deleterious effects of the environmental toxicant 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD; dioxin). However, the AhR is both ubiquitously-expressed and evolutionarily-conserved, suggesting that it evolved for purposes beyond strictly mediating responses to man-made environmental toxicants. There is growing evidence that the AhR is required for the maintenance of health, as it is implicated in physiological processes such as xenobiotic metabolism, organ development and immunity. Dysregulation of AhR expression and activity is also associated with a variety of disease states, particularly those at barrier organs such as the skin, gut and lungs. The lungs are particularly vulnerable to inhaled toxicants such as cigarette smoke. However, the role of the AhR in diseases such as chronic obstructive pulmonary disease (COPD)—a respiratory illness caused predominately by cigarette smoking—and lung cancer remains largely unexplored. This review will discuss the growing body of literature that provides evidence that the AhR protects the lungs against the damaging effects of cigarette smoke.
Highlights
The Aryl Hydrocarbon Receptor (AhR) is a ligand-activated transcription factor that is evolutionarily-conserved among multicellular organisms [1]
There is sufficient evidence to speculate that the AhR may lessen the susceptibility to chronic obstructive pulmonary disease (COPD) pathogenesis by attenuating cigarette smoke (CS)-induced pulmonary inflammation, oxidative stress, lung structural cell loss and bacterial infections that can trigger exacerbations (Figure 2)
The current body of literature regarding the AhR demonstrates the complexity and often contradictory nature of this signaling pathway and mechanisms associated with disease pathogenesis such as apoptosis, proliferation and senescence
Summary
The Aryl Hydrocarbon Receptor (AhR) is a ligand-activated transcription factor that is evolutionarily-conserved among multicellular organisms [1]. The basic domain enables binding of the AhR to DNA, whereas the HLH domain enables protein dimerization [4] This superfamily has been further subdivided phylogenetically into six classes (A-F). The AhR may mediate carcinogenicity induced by individual components of CS, such as 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) [18] and benzo[a]pyrene [19], it simultaneously protects against many of the pathogenic effects of CS in the lung [9,10,11,12,20]. Cigarette smoking is the primary cause of prevalent respiratory pathologies such as chronic obstructive pulmonary disease (COPD) and lung cancer, contributing to approximately 75% of both COPD [21] and lung cancer [22] cases The pathogenesis of these diseases involves the deregulation of cellular processes including cell survival, migration and proliferation. The focus of this review is to highlight the growing body of literature that demonstrates a role for the AhR in attenuating CS-induced lung injury, with particular emphasis on COPD
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a call
