Figure 2.

Mechanism of activation of the aryl hydrocarbon receptor (AhR). The AhR is abundantly expressed in lung, liver, and brain. It can be activated in many cell types, including epithelial cell, microglia, macrophage, B cell, T cell, etc. Without a ligand, AhR is inactivated in the cytoplasm as a part of a complex with heat shock protein (HSP)90, AhR-interacting protein (AIP), and p23. After binding with an exo/endogenous ligand, the AhR will be activated and translocates to the nucleus to interact with AhR nuclear translocator (ARNT) and simultaneously detaches from the complex. The AhR/ARNT heterodimer finally binds to the dioxin-response elements (DREs), which is called the promoter region of target genes [classical target genes include cytochrome P450 (Cyp)1a1, Cyp1a2, Cyp1b1, and AHRR], to promote transcriptional activation.