Ah receptor and NF-kappaB interactions, a potential mechanism for dioxin toxicity.
The Ah receptor (AhR) mediates many of the toxic responses induced by polyhalogenated and polycyclic hydrocarbons (PAHs) which are ubiquitous environmental contaminants causing toxic responses in human and wildlife. NF-kappaB is a pleiotropic transcription factor controlling many physiological functions adversely affected by PAHs, including immune suppression, thymus involution, hyperkeratosis, and carcinogenesis. Here, we show physical interaction and mutual functional repression between AhR and NF-kappaB. This mutual repression may provide an underlying mechanism for many hitherto poorly understood PAH-induced toxic responses, and may also provide a mechanistic explanation for alteration of xenobiotic metabolism by cytokines and compounds that regulate NF-kappaB.
Tian
Y
Y
Department of Environmental and Community Medicine, University of Medicine and Dentistry of New Jersey-Robert Wood Johnson Medical School, Piscataway, New Jersey 08854, USA.
Ke
S
S
Denison
M S
MS
Rabson
A B
AB
Gallo
M A
MA
D000818:Animals; D001483:Base Sequence; D019556:COS Cells; D019363:Cytochrome P-450 CYP1A1 / Q000235:genetics; D019388:Cytochrome P-450 CYP1A2 / Q000235:genetics; D017931:DNA Primers; D015971:Gene Expression Regulation, Enzymologic / Q000187:drug effects; D051379:Mice; D016328:NF-kappa B / Q000378:metabolism*; D000072317:Polychlorinated Dibenzodioxins / Q000633:toxicity*; D011485:Protein Binding; D018336:Receptors, Aryl Hydrocarbon / Q000378:metabolism*; D014407:Tumor Cells, Cultured
D017931:DNA Primers; D016328:NF-kappa B; D000072317:Polychlorinated Dibenzodioxins; D018336:Receptors, Aryl Hydrocarbon; D019363:Cytochrome P-450 CYP1A1; D019388:Cytochrome P-450 CYP1A2