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A Nuclear Receptor Atlas: macrophage activation
Grant D Barish1, Michael Downes, William A Alaynick
1Howard Hughes Medical Institute, The Salk Institute for Biological Studies, P.O. Box 85800, San Diego, California 92186-5800, USA.
Molecular Endocrinology (Baltimore, Md.)
|July 30, 2005
Summary
Macrophage activation involves a network of 28 nuclear receptors, with distinct temporal patterns for lipopolysaccharide and interferon gamma. This reveals key regulatory cascades and potential therapeutic targets for inflammatory diseases.
Area of Science:
- Immunology and Molecular Biology
- Innate Immunity and Inflammation
Background:
- Macrophage activation is crucial for innate immunity and implicated in inflammatory diseases like atherosclerosis.
- Understanding nuclear receptor involvement in macrophage activation is key to controlling inflammation.
Purpose of the Study:
- To comprehensively assess changes in murine nuclear receptor superfamily expression during macrophage activation.
- To identify nuclear receptors involved in macrophage activation by lipopolysaccharide (LPS) and interferon gamma (IFN-γ).
Main Methods:
- Quantitative real-time PCR (qPCR) was used to analyze the expression of 49 nuclear receptor superfamily members.
- Bone marrow-derived macrophages were activated using LPS and IFN-γ.
Main Results:
- A network of 28 nuclear receptors was identified in activated macrophages.
- Over half of these receptors exhibited distinct temporal expression patterns in three phases, unique to each activator.
- Specific early-acting receptors for LPS were identified as late markers for IFN-γ, demonstrating precise serial expression.
Conclusions:
- Macrophage activation involves intricate, temporally regulated nuclear receptor networks.
- These findings highlight a genome-wide regulatory process initiated within minutes.
- The identified nuclear receptors represent potential therapeutic targets for modulating inflammatory responses.