title: Metabolic-epigenetic crosstalk in macrophage activation.
abstract: Epigenetic enzymes are emerging as crucial controllers of macrophages, innate immune cells that determine the outcome of many inflammatory diseases. Recent studies demonstrate that the activity of particular chromatin-modifying enzymes is regulated by the availability of specific metabolites like acetyl-coenzyme A, S-adenosylmethionine, α-ketoglutarate, nicotinamide adenine dinucleotide and polyamines. In this way chromatin-modifying enzymes could sense the macrophage's metabolic status and translate this into gene expression and phenotypic changes. Importantly, distinct macrophage activation subsets display particular metabolic pathways. IFNγ/lipopolysaccharide-activated macrophages (MIFNγ/LPS or M1) display high glycolysis, which directly drives their inflammatory phenotype. In contrast, oxidative mitochondrial metabolism and enhanced polyamine production are hallmarks and requirements for IL-4-induced macrophage activation (MIL-4 or M2). Here we report how epigenetics could serve as a bridge between altered macrophage metabolism, macrophage activation and disease.
authors.affiliation: Experimental Vascular Biology, Department of Medical Biochemistry, Academic Medical Center, University of Amsterdam, Meibergdreef 9, 1105AZ, Amsterdam, The Netherlands.
authors.forename: Jeroen
authors.initials: J
authors.lastname: Baardman
authors.affiliation: Experimental Vascular Biology, Department of Medical Biochemistry, Academic Medical Center, University of Amsterdam, Meibergdreef 9, 1105AZ, Amsterdam, The Netherlands.
authors.forename: Iris
authors.initials: I
authors.lastname: Licht
authors.affiliation: Experimental Vascular Biology, Department of Medical Biochemistry, Academic Medical Center, University of Amsterdam, Meibergdreef 9, 1105AZ, Amsterdam, The Netherlands.
authors.forename: Menno P J
authors.initials: MP
authors.lastname: de Winther
authors.affiliation: Experimental Vascular Biology, Department of Medical Biochemistry, Academic Medical Center, University of Amsterdam, Meibergdreef 9, 1105AZ, Amsterdam, The Netherlands.
authors.forename: Jan
authors.initials: J
authors.lastname: Van den Bossche
mesh_terms: D000105:Acetyl Coenzyme A / Q000378:metabolism; D000107:Acetylation; D002843:Chromatin / Q000737:chemistry / Q000187:drug effects / Q000378:metabolism; D044127:Epigenesis, Genetic; D006019:Glycolysis / Q000187:drug effects / Q000235:genetics; D006655:Histone Deacetylases / Q000235:genetics / Q000276:immunology / Q000378:metabolism*; D006657:Histones / Q000235:genetics / Q000378:metabolism; D006801:Humans; D007113:Immunity, Innate; D007371:Interferon-gamma / Q000494:pharmacology; D015847:Interleukin-4 / Q000494:pharmacology; D047908:Intracellular Signaling Peptides and Proteins / Q000235:genetics / Q000276:immunology / Q000378:metabolism*; D007527:Isoenzymes / Q000235:genetics / Q000276:immunology / Q000378:metabolism; D007656:Ketoglutaric Acids / Q000378:metabolism; D008070:Lipopolysaccharides / Q000494:pharmacology; D008262:Macrophage Activation / Q000187:drug effects; D008264:Macrophages / Q000187:drug effects / Q000276:immunology / Q000378:metabolism*; D006899:Mixed Function Oxygenases / Q000235:genetics / Q000276:immunology / Q000378:metabolism*; D009243:NAD / Q000378:metabolism; D010085:Oxidative Phosphorylation / Q000187:drug effects; D011073:Polyamines / Q000378:metabolism; D011484:Protein-Arginine N-Methyltransferases / Q000235:genetics / Q000276:immunology / Q000378:metabolism*; D011518:Proto-Oncogene Proteins / Q000235:genetics / Q000276:immunology / Q000378:metabolism*; D012097:Repressor Proteins / Q000235:genetics / Q000276:immunology / Q000378:metabolism*; D012436:S-Adenosylmethionine / Q000378:metabolism
chemical_list: D002843:Chromatin; C411744:DMAP1 protein, human; D006657:Histones; C508598:IL4 protein, human; D047908:Intracellular Signaling Peptides and Proteins; D007527:Isoenzymes; D007656:Ketoglutaric Acids; D008070:Lipopolysaccharides; D011073:Polyamines; D011518:Proto-Oncogene Proteins; D012097:Repressor Proteins; D009243:NAD; D015847:Interleukin-4; D000105:Acetyl Coenzyme A; D012436:S-Adenosylmethionine; D007371:Interferon-gamma; D006899:Mixed Function Oxygenases; C462539:TET1 protein, human; C077013:PRMT2 protein, human; D011484:Protein-Arginine N-Methyltransferases; D006655:Histone Deacetylases
keywords: chromatin-modifying enzymes; epigenetics; histone acetylation and methylation; inflammation; macrophages; metabolism