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Macrophage polarization and meta-inflammation

Published:November 03, 2017DOI:https://doi.org/10.1016/j.trsl.2017.10.004
      Chronic overnutrition and obesity induces low-grade inflammation throughout the body. Termed “meta-inflammation,” this chronic state of inflammation is mediated by macrophages located within the colon, liver, muscle, and adipose tissue. A sentinel orchestrator of immune activity and homeostasis, macrophages adopt variable states of activation as a function of time and environmental cues. Meta-inflammation phenotypically skews these polarization states and has been linked to numerous metabolic disorders. The past decade has revealed several key regulators of macrophage polarization, including the signal transducer and activator of transcription family, the peroxisome proliferator–activated receptor gamma, the CCAAT–enhancer-binding proteins (C/EBP) family, and the interferon regulatory factors. Recent studies have also suggested that microRNAs and long noncoding RNA influence macrophage polarization. The pathogenic alteration of macrophage polarization in meta-inflammation is regulated by both extracellular and intracellular cues, resulting in distinct secretome profiles. Meta-inflammation-altered macrophage polarization has been linked to insulin insensitivity, atherosclerosis, inflammatory bowel disease, cancer, and autoimmunity. Thus, further mechanistic exploration into the skewing of macrophage polarization promises to have profound impacts on improving global health.

      Abbreviations:

      AGO (Argonaute), ARG1 (arginase1), ATM (adipose tissue macrophage), BAT (brown adipose tissue), BMDM (bone marrow derived macrophage), C/EBP (CCAAT-enhancer-binding proteins), CCL2 (C-C Motif Chemokine Ligand 2), CCR2 (C-C Motif Chemokine Receptor 2), CLS (crown-like structures), DAMPs (damage-associated molecular patterns), DNMT (DNA methyltransferase), DUSP1 (dual specificity protein phosphatase 1), FFA (free fatty acids), GLP-1 (Glucagon-like peptide-1), GVHD (graft-vs-host 541 diseases), IBD (Inflammatory Bowel Disease), IFN (interferon), IFNγ (interferon gamma), IKKβ (IkB kinase β), IL (interleukin), LPS (lipopolysaccharide), IRE1α (inositol-requiring enzyme 1α), IRFs (Interferon regulatory factors), ISGF3 (IFN-stimulated gene factor 3), JAK (Janus Kinase), JNK (c-Jun N-terminal kinase), lncRNA (long non-coding RNAs), LXR (liver X receptors), MAPK (Mitogen-Activated Protein Kinase), MCP-1 (monocyte chemoattractant protein-1), MCPIP (MCP-1-induced protein), miRNA (microRNA), MNP (mononuclear phagocytes), MSR1 (Macrophage Scavenger Receptor 1), NAFLD (nonalcoholic fatty liver disease), NFAT5 (Nuclear Factor of Activated T-Cells 5), NFκB (nuclear factor kappa-light-chain-enhancer of activated B cells), NO (nitric oxide), PC (phosphatidylcholine), PDGF (platelet derived growth factor), PE (phosphatidylethoanolamine), Pknox1 (PBX/Knotted 1 Homeobox 1), PPARγ (Peroxisome Proliferator-Activated Receptor gamma), RASA1 (RAS p21 Protein Activator 1), ROS (reactive oxygen species), RXRα (retinoid X receptor), S100A8 (S100 calcium-binding protein A8), SERCA (sarco/endoplasmic reticulum calcium-ATPase), SHIP1 (Phosphatidylinositol-3,4,5-trisphosphate 5-phosphatase 1), SOCS1 (suppressor of cytokine signaling 1), STAT (signal transducer and activator of transcription), T2D (type 2 diabetes), TAB2 (TGF-β Activated Kinase 1/MAP3K7 Binding Protein 2), TGF-β (transforming growth factor beta), TLR4 (Toll-like receptor 4), TNFa (tumor necrosis factor a), Tregs (T regulator cells), UCP1 (uncoupling protein-1), WAT (White adipose tissue)
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