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A Nuclear Receptor Atlas: Macrophage Activation

Howard Hughes Medical Institute (G.D.B., M.D., W.A.A., R.T.Y., C.B.O., R.M.E.), Gene Expression Laboratory, The Salk Institute for Biological Studies, La Jolla, California 92037; Division of Endocrinology and Metabolism (G.D.B.), Department of Medicine, University of California, San Francisco, California 94121; Biomedical Sciences Graduate Program (W.A.A.), University of California, San Diego, La Jolla, California 92093; and Howard Hughes Medical Institute and Department of Pharmacology (A.L.B., D.J.M.), University of Texas Southwestern Medical Center, Dallas, Texas 75390

Address all correspondence and requests for reprints to: Ronald M. Evans, Ph.D., Howard Hughes Medical Institute, The Salk Institute for Biological Studies, P.O. Box 85800, San Diego, California 92186-5800. E-mail: evans{at}salk.edu.

Macrophage activation is an essential cellular process underlying innate immunity, enabling the body to combat bacteria and other pathogens. In addition to host defense, activated macrophages play a central role in atherogenesis, autoimmunity, and a variety of inflammatory diseases. As members of the Nuclear Receptor Signaling Atlas (NURSA) program, we employed quantitative real-time PCR (qPCR) to provide a comprehensive assessment of changes in expression of the 49 members of the murine nuclear receptor superfamily. In this study, we have identified a network of 28 nuclear receptors associated with the activation of bone marrow-derived macrophages by lipopolysaccharide or the prototypic cytokine interferon . More than half of this network is deployed in three intricate and highly scripted temporal phases that are unique for each activator. Thus, early receptors whose expression peaks within 4 h after lipopolysaccharide exposure, such as glucocorticoid receptor, peroxisome proliferator-activated receptor , and neuronal growth factor 1B, are found as late rising markers of the interferon cascade, occurring 16 h or later. The discovery of precise serial expression patterns reveals that macrophage activation is the product of an underlying process that impacts the genome within minutes and identifies a collection of new therapeutic targets for controlling inflammation by disruption of presumptive regulatory cascades.

NURSA Molecule Pages Link:

Nuclear Receptors:   DAX1  |  SHP  |  TRα  |  TRβ  |  RARα  |  RARβ  |  RARγ  |  PPARα  |  PPARδ  |  PPARγ  |  REV-ERBα  |  REV-ERBβ  |  RORα  |  RORβ  |  RORγ  |  LXRβ  |  LXRα  |  FXRα  |  FXRβ  |  VDR  |  PXR  |  CAR-β  |  TLX  |  PNR  |  HNF4α  |  HNF4γ  |  HNF4β  |  RXRα  |  RXRβ  |  RXRγ  |  TR2  |  TR4  |  COUP-TFI  |  COUP-TFII  |  EAR-2  |  ERα  |  ERβ  |  ERRα  |  ERRβ  |  ERRγ  |  GR  |  MR  |  PR  |  AR  |  NGFIB  |  NURR1  |  NOR1  |  SF-1  |  LRH-1  |  GCNF

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