The AhR-Nrf2 pathway in keratinocytes: on the road to chemoprevention?

The ligand-activated transcription factor AhR mediates the cutaneous stress response toward a variety of environmental noxae and is therefore currently of interest for modern preventive medicine. In this issue, Tsuji et al. identify the antifungal agent ketoconazole as an inducer of AhR signaling and the Nrf2 antioxidant response in human keratinocytes. Ketoconazole-stimulated nuclear translocation of Nrf2 and its cytoprotective effects against oxidative stress strongly depend on a functional AhR. This newly identified AhR-Nrf2 pathway opens up new opportunities to prevent and treat inflammatory skin diseases.