Effects mediated by LXR

Group leader: Dr. Annabel Fernández Valledor

Nuclear receptors are members of a superfamily of ligand-dependent transcription factors that regulate diverse aspects of development and homeostasis. Liver X receptors (LXR alfa and beta) represent a subset of the nuclear receptor superfamily that are regulated by certain oxidized forms of cholesterol (oxysterols) and intermediate products of the cholesterol biosynthetic pathway. LXRs exert important roles in lipid homeostasis. Some of the target genes for LXR participate actively in reverse choleterol transport from peripheral tissues to the liver. LXR action is important in preventing artery wall macrophages from converting into foam cells. Synthetic LXR agonists have been shown to effectively act as anti-atherogenic agents in murine models in vivo.

Recent studies have also shown that LXR agonists play an important role in the regulation of immune responses. On one side, LXR has anti-inflammatory effects by virtue of its capability to inhibit pro-inflammatory gene expression. This effect is similar to that of glucocorticoids that act through the glucocorticoid receptor (GR), although the mechanisms underlying these activities are not completely understood. On the other side, LXR agonists protect macrophages from programmed cell death, which is normally induced during bacterial infection.

Our goals are: a) to study patterns of gene expression regulated by LXR; b) to associate these patterns with effects of LXR agonists on macrophage function in the context of an immune response, and c) to study alternative effects of LXR ligands on certain specialized macrophage populations (microglia, osteoclasts, etc.) and on other cells of the immune system.