A MicroRNA Circuitry Links Macrophage Polarization to Metabolic Homeostasis
Macrophages play an important role in tissue repair and remodeling and innate immune response. Tissue macrophages are highly heterogeneous and can undergo two distinct programs of functional specification termed classical (M1) and alternative (M2) activation1,2. In response to signals elicited by bacterial infections, such as lipopolysaccharide (LPS) and interferon-γ (IFN-γ), macrophages adopt a pro-inflammatory phenotype and contribute to defense against invading pathogens through phagocytosis, bactericidal activity, and the secretion of pro-inflammatory cytokines and chemokines. In contrast, interleukin-4 (IL-4) and IL-13 promote alternative activation of macrophages that favors tissue remodeling and repair, parasite elimination, and tumor progression. At the molecular level, M1 and M2 macrophages express unique cell surface markers and secrete distinct sets of effector molecules. Classically activated macrophages secrete pro-inflammatory cytokines, such as tumor necrosis factor α (TNFα), IL-1β, and IL-6, and produces reactive oxygen species and nitric oxide, whereas alternatively activated macrophages preferentially synthesize anti-inflammatory cytokines such as IL-10 and have subdued pro-inflammatory cytokine gene expression. A balance between classical and alternative macrophage activation serves to maintain tissue homeostasis and host defense. (SELECT FULL TEXT TO CONTINUE)
- Received April 28, 2012.
- Accepted May 1, 2012.
- Copyright © 2012, American Heart Association, Inc. All rights reserved. Unauthorized use prohibited