美国哈佛公共健康学院Tiffany Horng研究组近期揭示了磷酸甘油穿梭酶GPD2在调节巨噬细胞炎症反应中的作用。该项研究成果发表在2019年9月出版的《自然—免疫学》上。

研究人员发现在由细菌脂多糖（LPS）激活的巨噬细胞中，线粒体3-磷酸甘油脱氢酶（GPD2）调节葡萄糖氧化以驱动炎症反应。GPD2是调控甘油磷酸盐穿梭的成员，可促进葡萄糖氧化，从而为乙酰辅酶A的产生、组蛋白的乙酰化和编码炎症介质的基因的诱导提供动力。虽然急性暴露于LPS会导致巨噬细胞活化，但长期暴露于LPS会触发对LPS的耐受，其中巨噬细胞会诱导免疫抑制以限制持续炎症的不利影响。炎症反应的转变受到GPD2的调节，GPD2协调氧化代谢的关闭；这限制了乙酰辅酶A在编码炎症介质的基因上的组蛋白乙酰化的功能发挥，因此有助于抑制炎症反应。因此，GPD2和甘油磷酸酯穿梭将微生物刺激的程度与葡萄糖氧化相结合，以平衡炎症反应的有益和有害作用。

据了解，巨噬细胞在微生物感染时被激活以协调炎症反应和宿主防御。

附：英文原文

Title: Glycerol phosphate shuttle enzyme GPD2 regulates macrophage inflammatory responses

Author: P. Kent Langston, Aya Nambu, Jonathan Jung, Munehiko Shibata, H. Ibrahim Aksoylar, Jiahui Lei, Peining Xu, Mary T. Doan, Helen Jiang, Michael R. MacArthur, Xia Gao, Yong Kong, Edward T. Chouchani, Jason W. Locasale, Nathaniel W. Synder, Tiffany Horng

Issue&Volume: Volume 20 Issue 9

Abstract: 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.

DOI: 10.1038/s41590-019-0453-7

Source:https://www.nature.com/articles/s41590-019-0453-7