Figure 3.

Integration of lipid metabolic and inflammatory signaling in macrophages by LXRs. Recognition of cytokines, bacterial components, or intact pathogens by their corresponding receptors initiates expression of proinflammatory genes (e.g., iNOS). Activation of the TLR3/4 receptors by these signals blocks LXR-dependent gene transcription and cholesterol efflux from macrophages via an IFN regulatory factor 3–dependent (IRF3-dependent) pathway. On the other hand, ligand activation of LXRs inhibits NF-κB–dependent induction of inflammatory gene expression. Intracellular bacteria induce LXRα expression, possibly through a NOD2-dependent pathway, and promote macrophage survival, through induction of Api6 (also known as AIM and SPα) and other targets.