A gut feeling of the PXR, PPAR and NF-kappaB connection.
Bowel diseases reveal the complex interplay of sensing and signalling pathways in maintaining healthy homeostasis of the intestine. Recent studies of the xenobiotic nuclear receptor, pregnane X receptor and the inflammatory mediator nuclear transcription factor kappaB (NF-kappaB) reveal a functional link between xenobiotic neutralization and inflammation and explain how certain xenobiotics can affect the immune response. Furthermore, another nuclear receptor, peroxisome proliferator-activated receptor gamma (PPAR gamma) has been shown to produce beneficial effects in experimental inflammatory bowel diseases by repression of NF-kappaB thereby reducing inflammation, whilst its close relative PPAR beta/delta appears at a central position in signalling pathways involved in the progression of colon cancer. Recently accumulated knowledge on the action of these nuclear receptors and NF-kappaB in intestinal homeostasis may provide the rationale for the development of innovative treatment strategies with selective receptor modulators.
Wahli
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Center for Integrative Genomics, National Research Center Frontiers in Genetics, University of Lausanne, Lausanne, Switzerland. walter.wahli@unil.ch
D002471:Cell Transformation, Neoplastic / Q000378:metabolism; D003110:Colonic Neoplasms / Q000503:physiopathology; D006801:Humans; D015212:Inflammatory Bowel Diseases / Q000503:physiopathology*; D016328:NF-kappa B / Q000502:physiology*; D047492:Peroxisome Proliferator-Activated Receptors / Q000502:physiology*; D000077297:Pregnane X Receptor; D011987:Receptors, Steroid / Q000502:physiology*; D015398:Signal Transduction; D015262:Xenobiotics / Q000633:toxicity
D016328:NF-kappa B; D047492:Peroxisome Proliferator-Activated Receptors; D000077297:Pregnane X Receptor; D011987:Receptors, Steroid; D015262:Xenobiotics