我们当前对糖代谢如何影响巨噬细胞中炎症通路的理解仍不全面。在这里，我们展示了糖原代谢是控制巨噬细胞介导的炎症反应的重要环节。IFN-γ/LPS处理会刺激巨噬细胞合成糖原，随后通过糖原分解生成葡萄糖-6-磷酸（G6P），进一步通过戊糖磷酸途径生成大量NADPH，从而保证炎症巨噬细胞存活所需的高水平还原型谷胱甘肽。同时，糖原代谢还会增加巨噬细胞中的UDPG水平和受体P2Y14的表达。UDPG/P2Y14信号通路不仅通过激活RARβ上调STAT1的表达，还通过下调磷酸酶TC45促进STAT1的磷酸化。阻断这一糖原代谢途径会干扰多种小鼠模型中的急性炎症反应。糖原代谢还调节脓毒症患者的炎症反应。这些研究结果表明，巨噬细胞中的糖原代谢是一个重要调控因子，并提示了可能用于治疗急性炎症疾病的策略。

英文摘要：

Our current understanding of how sugar metabolism affects inflammatory pathways in macrophages is incomplete. Here, we show that glycogen metabolism is an important event that controls macrophage-mediated inflammatory responses. IFN-γ/LPS treatment stimulates macrophages to synthesize glycogen, which is then channeled through glycogenolysis to generate G6P and further through the pentose phosphate pathway to yield abundant NADPH, ensuring high levels of reduced glutathione for inflammatory macrophage survival. Meanwhile, glycogen metabolism also increases UDPG levels and the receptor P2Y14 in macrophages. The UDPG/P2Y14 signaling pathway not only upregulates the expression of STAT1 via activating RARβ but also promotes STAT1 phosphorylation by downregulating phosphatase TC45. Blockade of this glycogen metabolic pathway disrupts acute inflammatory responses in multiple mouse models. Glycogen metabolism also regulates inflammatory responses in patients with sepsis. These findings show that glycogen metabolism in macrophages is an important regulator and indicate strategies that might be used to treat acute inflammatory diseases.

论文信息：

论文题目：Glycogen metabolism regulates macrophage-mediated acute inflammatory responses

期刊名称：Nature Communications

时间期卷：11, Article number: 1769(2020)

在线时间：2020年4月14日

DOI： doi.org/10.1038/s41467-020-15636-8

产品信息：

货号：C-005

规格：5ml

品牌：Liposoma

产地：荷兰

名称：Clodronate Liposomes