Metabolic-epigenetic crosstalk in macrophage activation
Metabolic-epigenetic crosstalk in macrophage activation
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DOI：
10.2217/epi.15.71
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发表时间：
2015-01-01
期刊：
影响因子：
3.8
通讯作者：
Van den Bossche, Jan
中科院分区：
文献类型：
--
作者：
Baardman, Jeroen;Licht, Iris;Van den Bossche, Jan
表观遗传酶正在成为巨噬细胞的关键控制器，巨噬细胞是决定许多炎症性疾病结果的先天免疫细胞。最近的研究表明，特定染色质修饰酶的活性受到特定代谢物（如乙酰辅酶 A、S-腺苷甲硫氨酸、α-酮戊二酸、烟酰胺腺嘌呤二核苷酸和多胺）的可用性的调节。通过这种方式，染色质修饰酶可以感知巨噬细胞的代谢状态，并将其转化为基因表达和表型变化。重要的是，不同的巨噬细胞激活子集显示出特定的代谢途径。 IFN γ/脂多糖激活的巨噬细胞（M-IFN γ/（LPS）或 M1）表现出高糖酵解，这直接驱动其炎症表型。相反，氧化线粒体代谢和增强的多胺产生是 IL-4 诱导的巨噬细胞激活（MIL-4 或 M2）的标志和要求。在这里，我们报告表观遗传学如何充当巨噬细胞代谢改变、巨噬细胞激活和疾病之间的桥梁。
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, alpha-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. IFN gamma/lipopolysaccharide-activated macrophages (M-IFN gamma/(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.