Nuclear Receptors as Regulators of Macrophage Homeostasis and Function

Abstract

Nuclear hormone receptors comprise a superfamily of ligand-dependent transcription factors that regulate diverse aspects of development and homeostasis. Several members of this superfamily play important roles in the regulation of inflammatory responses and lipid homeostasis in macrophages. These include the glucocorticoid receptor, which acts to inhibit inflammatory programs of gene expression in response to natural corticosteroids and synthetic anti-inflammatory agents such as dexamethasone, peroxisome proliferator-activated receptors (PPARs) that regulate fatty acid homeostasis and inflammation in response to endogenous eicosanoids, and liver X receptors (LXRs) that regulate cholesterol efflux in response to endogenous oxysterols. Recent progress in defining the physiological roles of these receptor systems in macrophages and understanding their mechanisms of action suggest that they may be important targets for the development of new classes of pharmaceuticals that will be useful for treating human diseases in which macrophages play critical pathogenic roles, such as atherosclerosis and arthritis.