我們當前對糖代謝如何影響巨噬細胞中炎癥通路的理解仍不全面。在這里，我們展示了糖原代謝是控制巨噬細胞介導的炎癥反應的重要環(huán)節(jié)。IFN-γ/LPS處理會刺激巨噬細胞合成糖原，隨后通過糖原分解生成葡萄糖-6-磷酸（G6P），進一步通過戊糖磷酸途徑生成大量NADPH，從而保證炎癥巨噬細胞存活所需的高水平還原型谷胱甘肽。同時，糖原代謝還會增加巨噬細胞中的UDPG水平和受體P2Y14的表達。UDPG/P2Y14信號通路不僅通過激活RARβ上調(diào)STAT1的表達，還通過下調(diào)磷酸酶TC45促進STAT1的磷酸化。阻斷這一糖原代謝途徑會干擾多種小鼠模型中的急性炎癥反應。糖原代謝還調(diào)節(jié)膿毒癥患者的炎癥反應。這些研究結果表明，巨噬細胞中的糖原代謝是一個重要調(diào)控因子，并提示了可能用于治療急性炎癥疾病的策略。

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.

論文信息：

論文題目：Glycogen metabolism regulates macrophage-mediated acute inflammatory responses

期刊名稱：Nature Communications

時間期卷：11, Article number: 1769(2020)

在線時間：2020年4月14日

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

產(chǎn)品信息：

貨號：C-005

規(guī)格：5ml

品牌：Liposoma

產(chǎn)地：荷蘭

名稱：Clodronate Liposomes