Aromatic hydrocarbon receptor status in the metabolism of xenobiotics under normal and pathophysiological conditions.

The aryl hydrocarbon receptor (AhR), a cytosolic protein belonging to the family of nuclear receptors, controls transcription of a wide range of structurally unrelated genes. To date, the most potent AhR ligand is 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD). Exposure to TCDD leads to a number of toxic effects, in particular to tumor promotion and immunosuppression. The function of AhR in cells and living organisms therefore seems to be of paramount importance. Its absence in AhR null mice, results in severe phenotypic abnormalities, such as liver half size with fibrosis, accumulation of retinoic acid and immune system insufficiency. An important role of AhR inheres in its transcriptional control of several biotransformation enzymes (CYP1A1/2,1B1). Hence AhR is the crucial factor in the regulation of xenobiotic metabolism. Under pathophysiological conditions, such as inflammation, the level and activity of the AhR target gene CYP1A is decreased. Thus it is likely, that mediators and/or products of inflammation affect AhR function. This review deals with the role of AhR in xenobiotic metabolism under normal and pathophysiological conditions, with respect to inflammation in particular.