Mechanisms
Inflammatory macrophages selectively lose the LXR-driven induction of CETP seen in noninflammatory cells, even as ABCA1 and ABCG1 induction persist (Arterioscler Thromb Vasc Biol 2009)
Original title: Liver X receptor-mediated induction of cholesteryl ester transfer protein expression is selectively impaired in inflammatory macrophages
Cholesteryl ester transfer protein (CETP) is a target gene for the liver X receptor (LXR), and the authors examined this regulation across macrophage differentiation and inflammation. The LXR agonist T0901317 increased CETP, PLTP and ABCA1 mRNA in bone marrow-derived macrophages from human CETP transgenic mice, and markedly increased CETP mRNA and production in human differentiated macrophages, but had no effect in human peripheral blood monocytes. In inflammatory mouse and human macrophages, LXR-mediated CETP gene upregulation was inhibited, even though ABCA1, ABCG1 and SREBP1c induction were maintained. This inhibition was independent of lipid loading, since oxidized LDL still increased CETP production in noninflammatory macrophages with a synergistic effect from synthetic LXR agonists. LXR-mediated induction of human CETP is switched on during monocyte-to-macrophage differentiation, magnified by lipid loading, and selectively lost in inflammatory macrophages.
Original abstract
Objective: Cholesteryl ester transfer protein (CETP) is a target gene for the liver X receptor (LXR). The aim of this study was to further explore this regulation in the monocyte-macrophage lineage and its modulation by lipid loading and inflammation, which are key steps in the process of atherogenesis.
Methods And Results: Exposure of bone marrow-derived macrophages from human CETP transgenic mice to the T0901317 LXR agonist increased CETP, PLTP, and ABCA1 mRNA levels. T0901317 also markedly increased CETP mRNA levels and CETP production in human differentiated macrophages, whereas it had no effect on CETP expression in human peripheral blood monocytes. In inflammatory mouse and human macrophages, LXR-mediated CETP gene upregulation was inhibited, even though ABCA1, ABCG1, and SREBP1c inductions were maintained. The inhibition of CETP gene response to LXR agonists in inflammatory cells was independent of lipid loading (ie, oxidized LDL increased CETP production in noninflammatory macrophages with a synergistic effect of synthetic LXR agonists).
Conclusions: LXR-mediated induction of human CETP expression is switched on during monocyte-to-macrophage differentiation, is magnified by lipid loading, and is selectively lost in inflammatory macrophages, which suggests that inflammatory cells may not increase the circulating CETP pool on LXR agonist treatment.
Summary written by cetpinhibition.org from the published abstract; figures as published. Page updated 19 August 2026. Methods.