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.
Keywords:
chromatin-modifying enzymes; epigenetics; histone acetylation and methylation; inflammation; macrophages; metabolism.
Publication types
-
Research Support, Non-U.S. Gov't
MeSH terms
-
Acetyl Coenzyme A / metabolism
-
Acetylation
-
Chromatin / chemistry
-
Chromatin / drug effects
-
Chromatin / metabolism
-
Epigenesis, Genetic*
-
Glycolysis / drug effects
-
Glycolysis / genetics
-
Histone Deacetylases / genetics
-
Histone Deacetylases / immunology
-
Histone Deacetylases / metabolism*
-
Histones / genetics
-
Histones / metabolism
-
Humans
-
Immunity, Innate
-
Interferon-gamma / pharmacology
-
Interleukin-4 / pharmacology
-
Intracellular Signaling Peptides and Proteins / genetics
-
Intracellular Signaling Peptides and Proteins / immunology
-
Intracellular Signaling Peptides and Proteins / metabolism*
-
Isoenzymes / genetics
-
Isoenzymes / immunology
-
Isoenzymes / metabolism
-
Ketoglutaric Acids / metabolism
-
Lipopolysaccharides / pharmacology
-
Macrophage Activation / drug effects
-
Macrophages / drug effects
-
Macrophages / immunology
-
Macrophages / metabolism*
-
Mixed Function Oxygenases / genetics
-
Mixed Function Oxygenases / immunology
-
Mixed Function Oxygenases / metabolism*
-
NAD / metabolism
-
Oxidative Phosphorylation / drug effects
-
Polyamines / metabolism
-
Protein-Arginine N-Methyltransferases / genetics
-
Protein-Arginine N-Methyltransferases / immunology
-
Protein-Arginine N-Methyltransferases / metabolism*
-
Proto-Oncogene Proteins / genetics
-
Proto-Oncogene Proteins / immunology
-
Proto-Oncogene Proteins / metabolism*
-
Repressor Proteins / genetics
-
Repressor Proteins / immunology
-
Repressor Proteins / metabolism*
-
S-Adenosylmethionine / metabolism
Substances
-
Chromatin
-
DMAP1 protein, human
-
Histones
-
IL4 protein, human
-
Intracellular Signaling Peptides and Proteins
-
Isoenzymes
-
Ketoglutaric Acids
-
Lipopolysaccharides
-
Polyamines
-
Proto-Oncogene Proteins
-
Repressor Proteins
-
NAD
-
Interleukin-4
-
Acetyl Coenzyme A
-
S-Adenosylmethionine
-
Interferon-gamma
-
Mixed Function Oxygenases
-
TET1 protein, human
-
PRMT2 protein, human
-
Protein-Arginine N-Methyltransferases
-
Histone Deacetylases