304760.fig.005
Figure 5: Modulation of gene expression by PPARs and inflammatory transcription factors: transactivation and transrepression mechanisms. The activation of PPARs (a) and inflammatory transcription factors (b) modulates gene expression via specific response elements (RE), resulting mainly in the upregulation of proteins involved in several metabolic and inflammatory pathways, respectively. The two routes may connect through protein-protein interaction upstream to DNA-protein interaction (c). This transrepressive action of a pathway on the other is a basis for the anti-inflammatory/antioxidative properties of PPARs, and though less often mentioned, for the anti-PPAR properties of inflammatory/oxidative processes. Abbreviations: COX2, cyclooxygenase 2; ICAM, inducible cell adhesion molecule; PPRE, PPAR-responsive element; RXRα, retinoid acid X receptor α. The mechanisms by which metabolic changes and anti-inflammatory properties induced by PPARs interfere with the Warburg’s effect and cancer development are considered in the text.