The aryl hydrocarbon receptor links TH17-cell-mediated autoimmunity to environmental toxins

Leflunomide, flutamide, nimodipine, mexiletine, sulindac, tranilast, 4-hydroxytamoxifen, and omeprazole are pharmaceuticals previously characterized as aryl hydrocarbon receptor (AHR) agonists in various cell lines and animal models. In this study, the eight AHR-active pharmaceuticals were investigated in highly aggressive aryl hydrocarbon (Ah)-responsive BT474 and MDA-MB-468 breast cancer cell...

8β-Hydroxy-9(11),13-abietadien-12-one (1), an abietane diterpenoid and aryl hydrocarbon receptor (AhR) ligand, was synthesized in six steps from commercially available (+)-dehydroabietylamine (2). We used the hypervalent iodine catalyst phenyliodine dicarboxylate, a safer alternative to toxic organoselenide reagents, for oxidative dearomatization of ferruginol (7) compound 1. Compounds 1 2, as ...

The aryl hydrocarbon receptor (AHR) is a ligand-activated transcription factor that dimerizes with ARNT to mediate responses to compounds such as 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD). TCDD and other AHR agonists cause toxic responses in early life stages of fish, including the zebrafish, Danio rerio. The most well characterized target gene for the AHR/aryl hydrocarbon receptor nuclear tra...

The aryl hydrocarbon receptor (AhR), a transcription factor known for mediating xenobiotic toxicity, is expressed in B cells, which are known targets for environmental pollutants. However, it is unclear what the physiological functions of AhR in B cells are. We show here that expression of Ahr in B cells is up-regulated upon B-cell receptor (BCR) engagement and IL-4 treatment. Addition of a nat...

The Drosophila spineless (ss) gene encodes a basic-helix-loop-helix-PAS transcription factor that is required for proper specification of distal antennal identity, establishment of the tarsal regions of the legs, and normal bristle growth. ss is the closest known homolog of the mammalian aryl hydrocarbon receptor (Ahr), also known as the dioxin receptor. Dioxin and other aryl hydrocarbons bind ...

The aryl hydrocarbon receptor (AhR), a transcription factor of the bHLH/PAS family, has recently been demonstrated to regulate T cell differentiation. Whether AhR activation participates in allergic airway inflammation remains unknown. In the current study, using a non-eosinophilic asthma model, we demonstrate that 2, 3, 7, 8-tetrachlorodibenzo-P-dioxin (TCDD), a potent AhR ligand, reduced the ...

The aryl hydrocarbon receptor (AHR) is a ligand-activated transcription factor recognized for its role in xenobiotic metabolism. The physiologic function of AHR has expanded to include roles in immune regulation, organogenesis, mucosal barrier function, and the cell cycle. These functions are likely dependent upon ligand-mediated activation of the receptor. High-affinity ligands of AHR have bee...

The aryl hydrocarbon receptor (AhR) is a ligand-activated basic-helix-loop-helix transcription factor that binds polyaromatic hydrocarbons (PAH), such as 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD), and mediates their toxicity. Binding of PAH to AhR in the cytoplasm triggers a poorly defined transformation step of the receptor into a nuclear transcription factor. In this study, we show that the ...

The aryl hydrocarbon receptors (AHR) are bHLH-PAS domain containing transcription factors. In mammals, they mediate responses to environmental toxins such as 2, 3, 7, 8-tetrachlorodibenzo-p-dioxin (TCDD). Such functions of AHRs require a cofactor, the aryl hydrocarbon receptor nuclear translocator (ARNT), and the cytoplasmic chaperonins HSP90 and XAP2. AHR homologs have been identified througho...