A gut feeling of the PXR, PPAR and NF-κB connection

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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-κB) 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 γ (PPARγ) has been shown to produce beneficial effects in experimental inflammatory bowel diseases by repression of NF-κB thereby reducing inflammation, whilst its close relative PPARβ/δ 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-κB in intestinal homeostasis may provide the rationale for the development of innovative treatment strategies with selective receptor modulators.

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