Ah receptor and NF-kappa B interactions, a potential mechanism for dioxin toxicity

The Ah receptor (AhR) mediates many of the toxic responses induced by polyh alogenated and polycyclic hydrocarbons (PAHs) which are ubiquitous environm ental contaminants causing toxic responses in human and wildlife. NF-kappa B is a pleiotropic transcription factor controlling many physiological func tions adversely affected by PAHs, including immune suppression, thymus invo lution, hyperkeratosis, and carcinogenesis. Here, we show physical interact ion and mutual functional repression between AhR and NF-kappa B, This mutua l repression may provide an underlying mechanism for many hitherto poorly u nderstood PAM-induced toxic responses, and may also provide a mechanistic e xplanation for alteration of xenobiotic metabolism by cytokines and compoun ds that regulate NF-kappa B.