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J Biol Chem, Vol. 274, Issue 1, 510-515, January 1, 1999

Ah Receptor and NF-kappa B Interactions, a Potential Mechanism for Dioxin Toxicity

Yanan TianDagger , Sui KeDagger , Michael. S. Denison§, Arnold B. Rabsonparallel , and Michael A. GalloDagger parallel

From the Dagger  Department of Environmental and Community Medicine, Environmental & Occupational Health Sciences Institute, University of Medicine and Dentistry of New Jersey-Robert Wood Johnson Medical School, Piscataway, New Jersey 08854, the § Department of Environmental Toxicology, University of California, Davis, California 95616, the  Center for Advanced Biotechnology and Medicine, Department of Molecular Genetics and Microbiology, University of Medicine and Dentistry of New Jersey-Robert Wood Johnson Medical School, Piscataway, New Jersey 08854, and the parallel  Cancer Institute of New Jersey, New Brunswick, New Jersey 08901

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-kappa B 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-kappa B. 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-kappa B.


Copyright © 1999 by The American Society for Biochemistry and Molecular Biology, Inc.
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