脂多糖
炎症
生物化学
乙酰化
脱氢酶
促炎细胞因子
生物
化学
细胞生物学
酶
免疫学
基因
作者
P. Kent Langston,Aya Nambu,Jonathan Jung,Masakazu Shibata,Halil‐Ibrahim Aksoylar,Jiahui Lei,Peining Xu,Mary T. Doan,Hairong Jiang,Michael R. MacArthur,Xia Gao,Yong Kong,Edward T. Chouchani,Jason W. Locasale,Nathaniel W. Snyder,Tiffany Horng
出处
期刊:Nature Immunology
[Springer Nature]
日期:2019-08-05
卷期号:20 (9): 1186-1195
被引量:130
标识
DOI:10.1038/s41590-019-0453-7
摘要
Macrophages are activated during microbial infection to coordinate inflammatory responses and host defense. Here we find that in macrophages activated by bacterial lipopolysaccharide (LPS), mitochondrial glycerol 3-phosphate dehydrogenase (GPD2) regulates glucose oxidation to drive inflammatory responses. GPD2, a component of the glycerol phosphate shuttle, boosts glucose oxidation to fuel the production of acetyl coenzyme A, acetylation of histones and induction of genes encoding inflammatory mediators. While acute exposure to LPS drives macrophage activation, prolonged exposure to LPS triggers tolerance to LPS, where macrophages induce immunosuppression to limit the detrimental effects of sustained inflammation. The shift in the inflammatory response is modulated by GPD2, which coordinates a shutdown of oxidative metabolism; this limits the availability of acetyl coenzyme A for histone acetylation at genes encoding inflammatory mediators and thus contributes to the suppression of inflammatory responses. Therefore, GPD2 and the glycerol phosphate shuttle integrate the extent of microbial stimulation with glucose oxidation to balance the beneficial and detrimental effects of the inflammatory response.
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