Identification of PLTP as an LXR target gene and apoE as an FXR target gene reveals overlapping targets for the two nuclear receptors

Affymetrix microarray data and Northern blot assays demonstrated that phospholipid tran fer protein (PLTP) was induced 6-fold when either murine or human macrophages were incubated in the presence of ligands for the liver X receptor (LXR) and the retinoid X receptor. Two functional LXR response elements (LXREs) were identified and characterized in the proximal promoter of the human PLTP gene. One LXRE corresponds to a traditional direct repeat separated by 4 bp. However, the second LXRE is novel in that it corresponds to an inverted repeat separated by 1 bp, and is identical to the farnesoid X receptor response element. These studies demonstrate that PLTP is a direct target for activated LXR and farnesoid X receptor (FXR). In addition, apolipoprotein E (apoE), a known LXR target gene in macrophages, was shown to be activated in liver cells by FXR ligands. Taken together, the current data suggest that a small number of genes that currently include PLTP, apoE, and apoC-II, are induced in macrophages by activated LXR and in liver by activated FXR.