Regulation of Xenobiotic Sensor PXR and AhR by NF-kappa B and Its Roles in Xenobiotic Detoxification and Inflammation-Associated Carcinogenesis
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2010. Elsevier Ltd All rights reserved. Recent studies reveal cross talks between nuclear factor-?B (NF-?B)-regulated inflammatory pathways and nuclear receptor-regulated pathways. These interactions are mediated at least in part by the interactions between various NF-?B family proteins and a group of ligand-dependent transcription factors with xenobiotic sensor functions including pregnane X receptor (PXR) and aryl hydrocarbon receptor (AhR). These interactions are particularly important in tissues/organs that come in contact with toxicants, such as the gastrointestinal (GI) tract. Research on these interactions is important for understanding diseases including liver and colon carcinogenesis for which inflammation is a significant risk factor. In addition to regulation of detoxification pathways, novel functions of PXR have recently been discovered, which include regulation of cell proliferation, apoptosis, and cancer cell growth. Collectively, these results suggest a multitude of PXR functions in reducing mutagenic exposure through metabolic detoxification as well as in regulating cell proliferation and cancer growth. PXR, AhR, and NF-?B are transcriptional factors that can be regulated by various natural and synthetic ligands, and research on their interactions may provide a basis for therapeutic and preventive applications of compounds that target these proteins for treatment and prevention of human diseases.
