Transcriptional Regulation of Human CYP27 Integrates Retinoid, Peroxisome Proliferator-Activated Receptor, and Liver X Receptor Signaling in Macrophages

• DOI: 10.1128/mcb.24.18.8154-8166.2004
• Publication Date: 2004-08-31T00:08:05Z
• Authors: Attila Szanto; Szilvia Benko; Istvan Szatmari; Balint L. Balint; Ibolya Furtos; Ralph Rühl; Sandor Molnar; Laszlo Csiba; Rita Garuti; Sebastiano Calandra; Hanna Larsson; Ulf Diczfalusy; Laszlo Nagy
• Keywords: Liver X receptor; Retinoid X receptor

Cholesterol uptake and efflux are key metabolic processes associated with macrophage physiology atherosclerosis. Peroxisome proliferator-activated receptor gamma (PPARγ) liver X alpha (LXRα) have been linked to the regulation of these processes. It remains be identified how activation receptors is connected regulated by endogenous lipid molecules. We CYP27, a p450 enzyme, as link between retinoid, PPARγ, LXR signaling. show that human CYP27 gene under coupled retinoids ligands PPARs via PPAR-retinoic acid response element in its promoter. Induction enzyme's expression results an increased level 27-hydroxycholesterol upregulation LXR-mediated Upregulated activity also leads LXR-independent elimination metabolites alternative means cholesterol efflux. Moreover, macrophage-rich atherosclerotic lesions retinoid-, PPARγ-, LXR-regulated enhanced levels. Our findings suggest nuclear receptor-regulated likely integrator retinoic receptor-PPARγ-LXR signaling, relying on natural contributing metabolism macrophages.