title: The aryl hydrocarbon receptor: a multifunctional chemical sensor for host defense and homeostatic maintenance.
abstract: The aryl hydrocarbon receptor (AHR) is a pivotal chemical sensor that transduces extrinsic and intrinsic signals into cellular responses. AHR was originally thought to be involved in not only drug metabolism but also carcinogenic and toxicological responses against environmental contaminants, such as 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) and polycyclic aromatic hydrocarbons. However, recent studies demonstrate that the AHR plays multiple intrinsic roles in host defense and homeostasis as well, including immunity, stem cell maintenance, and cell differentiation, upon binding with an increasing number of newly defined dietary, cellular, and microbe-derived ligands. In addition, AHR is a convergence point for several signaling cascades, which may be involved in the diverse diseases caused by binding of the persistent ligand TCDD with extremely high affinity to AHR. A comprehensive understanding of physiological and pathological processes initiated by endogenous AHR agonists and antagonists may allow for the therapeutic regulation of AHR activity. Thus, the AHR can be a valuable diagnostic marker and therapeutic target for human diseases.
authors.affiliation: Research Institute for Clinical Oncology, Saitama Cancer Center, 818 Komuro, Ina-machi, Saitama 362-0806, Japan.
authors.forename: Kaname
authors.initials: K
authors.lastname: Kawajiri
authors.affiliation: Medical Research Institute, Tokyo Medical and Dental University, 1-5-45 Yushima, Bunkyo-ku, Tokyo 113-8510, Japan.
authors.forename: Yoshiaki
authors.initials: Y
authors.lastname: Fujii-Kuriyama
mesh_terms: D051792:Basic Helix-Loop-Helix Proteins / Q000378:metabolism; D002454:Cell Differentiation; D003577:Cytochrome P-450 Enzyme System / Q000378:metabolism; D004147:Dioxins / Q000378:metabolism; D006706:Homeostasis; D006801:Humans; D008024:Ligands; D058990:Molecular Targeted Therapy; D018336:Receptors, Aryl Hydrocarbon / Q000819:agonists / Q000037:antagonists & inhibitors / Q000276:immunology* / Q000502:physiology*; D015398:Signal Transduction; D013234:Stem Cells / Q000166:cytology
chemical_list: D051792:Basic Helix-Loop-Helix Proteins; D003577:Cytochrome P-450 Enzyme System; D004147:Dioxins; D008024:Ligands; D018336:Receptors, Aryl Hydrocarbon; C066841:2,3,7,8-tetrabromodibenzo-4-dioxin
keywords: P450; TCDD; bHLH-PAS transcription factor; immunity; microbes