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This version published online on July 28, 2005
Molecular Endocrinology, doi:10.1210/me.2004-0529
A more recent version of this article appeared on October 1, 2005
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*Substance via MeSH

Submitted on December 22, 2004
Accepted on May 31, 2005

A Nuclear Receptor Atlas: Macrophage Activation

Grant D. Barish, Michael Downes, William A. Alaynick, Ruth T. Yu, Corinne B. Ocampo, Angie L. Bookout, David J. Mangelsdorf, and Ronald M. Evans*

Howard Hughes Medical Institute, Gene Expression Laboratory, The Salk Institute for Biological Studies, La Jolla, CA 92037; Division of Endocrinology and Metabolism, Department of Medicine, University of California, San Francisco, CA 94121; Biomedical Sciences Graduate Program, University of California, San Diego, La Jolla, CA 92093; Howard Hughes Medical Institute and Department of Pharmacology, University of Texas Southwestern Medical Center, Dallas, Texas 75390

* To whom correspondence should be addressed. 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 (LPS) or the prototypic cytokine interferon gamma (IFN-{gamma}). 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 four hours following LPS exposure, such as glucocorticoid receptor (GR), peroxisome proliferator-activated receptor gamma (PPAR{gamma}), and neuronal growth factor 1B (NGFIB), are found as late rising markers of the IFN-{gamma} 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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