A Nuclear Receptor Atlas: macrophage activation.
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 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 4 h after lipopolysaccharide exposure, such as glucocorticoid receptor, peroxisome proliferator-activated receptor gamma, and neuronal growth factor 1B, are found as late rising markers of the interferon 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.
Barish
Grant D
GD
Howard Hughes Medical Institute, The Salk Institute for Biological Studies, P.O. Box 85800, San Diego, California 92186-5800, USA.
Downes
Michael
M
Alaynick
William A
WA
Yu
Ruth T
RT
Ocampo
Corinne B
CB
Bookout
Angie L
AL
Mangelsdorf
David J
DJ
Evans
Ronald M
RM
D000818:Animals; D030562:Databases, Protein; D020869:Gene Expression Profiling; D066298:In Vitro Techniques; D018836:Inflammation Mediators / Q000378:metabolism; D007371:Interferon-gamma / Q000494:pharmacology; D008070:Lipopolysaccharides / Q000494:pharmacology; D008262:Macrophage Activation / Q000187:drug effects; D008264:Macrophages / Q000187:drug effects / Q000276:immunology / Q000502:physiology; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D016133:Polymerase Chain Reaction; D018160:Receptors, Cytoplasmic and Nuclear / Q000235:genetics / Q000276:immunology*; D011994:Recombinant Proteins; D015398:Signal Transduction
D018836:Inflammation Mediators; D008070:Lipopolysaccharides; D018160:Receptors, Cytoplasmic and Nuclear; D011994:Recombinant Proteins; D007371:Interferon-gamma