干白素-6的经典和跨信号利用葡萄糖代谢重编程来实现抗炎或促炎作用
Shilei Xu1, Ke-Qiong Deng2, Chengbo Lu3
1Department of General Surgery, The Third Affiliated Hospital, Sun Yat-Sen University, Guangzhou, Guangdong 510530, China.
Metabolism: clinical and experimental
|March 4, 2024
概括
介质素-6 (IL-6) 经典信号通过氧化酸化促进抗炎反应,而IL-6转信号通过无氧糖解驱动促炎作用,揭示了不同的代谢途径.
科学领域:
- 免疫学 免疫学 免疫学
- 代谢途径 代谢途径
- 细胞信号传递 细胞信号传递
背景情况:
- 介质素-6 (IL-6) 具有抗炎和促炎作用,通过不同的信号通路进行介导:经典信号和转信号.
- 精确的下游分子机制区分这些IL-6信号通路,特别是关于细胞代谢,仍然在很大程度上未被阐明.
研究的目的:
- 研究IL-6经典信号传递和IL-6跨信号传递对细胞能量代谢的差异性影响.
- 为了确定每个IL-6信号模式所调节的特定分子参与者和代谢途径.
- 阐明这些代谢变化如何导致不同的炎症结果和T细胞分化.
主要方法:
- 分析IL-6介导的葡萄糖代谢,重点关注涉及STAT3,HK2和VDAC1.1的蛋白质复合体的形成.
- 研究线粒体转位和STAT3与PDK1在经典IL-6信号传递中的相互作用.
- 检查SIRT2和LDHA相互作用及其对IL-6转信号中的STAT3修饰的影响.
主要成果:
- IL-6激活葡萄糖溶解,经典的信号引导葡萄糖流向氧化酸化 (OxPhos) 和转信号向厌氧葡萄糖溶解.
- 经典的IL-6信号传递涉及线粒体STAT3-PDK1相互作用,在Ser727促进PDHA脱和STAT3酸化,驱动调节性T细胞分化.
- IL-6跨信号涉及SIRT2-LDHA相互作用,导致LDHA脱乙和STAT3乙化/酸化在Tyr705,促进Th17细胞分化.
结论:
- 通过OxPhos,IL-6经典信号传递通过增强能量代谢来赋予抗炎性质.
- IL-6跨信号通过将细胞能量代谢转移到无氧糖解来促进促炎功能.
- 通过IL-6信号通路的明显代谢重编程决定了特定的T细胞分化和炎症反应.
相关概念视频
Insulin: The Receptor and Signaling Pathways
1.2K
Insulin action is mediated through a receptor tyrosine kinase, akin to the IGF-1 receptor. The number of receptors per cell varies significantly, from 40 on erythrocytes to 300,000 on adipocytes and hepatocytes. The insulin receptor consists of linked α/β subunit dimers, forming a heterotetramer glycoprotein with two extracellular α subunits and two β subunits spanning the membrane. The α subunits inhibit the inherent tyrosine kinase activity of the β subunits, but...
1.2K
Hormones Regulating Blood Glucose
3.3K
Insulin is released by beta cells of the pancreas when blood glucose levels are high. It facilitates glucose absorption and utilization in insulin-dependent cells with insulin receptors on their plasma membranes. Insulin promotes glucose uptake by increasing the number of glucose transport proteins in the cell membrane, allowing glucose to enter the cell. As a result, glucose utilization and ATP production are enhanced.
In addition to accelerating glucose uptake and utilization, insulin has...
In addition to accelerating glucose uptake and utilization, insulin has...
3.3K
The JAK-STAT Signaling Pathway
8.9K
Several cytokine receptors have tightly bound Janus kinase or JAK proteins attached at their cytosolic tail. Small signaling molecules such as cytokines, growth hormones, or prolactins bind to the cytokine receptors and initiate their dimerization. The dimerization brings the cytosolic JAKs together that trans-phosphorylate and activates each other. The activated JAKs now phosphorylate cytosolic tails of the cytokine receptors, which serve as binding sites for adaptor proteins such as SH2...
8.9K
Glucose Homeostasis: Pancreatic Islets and Insulin Secretion
1.3K
The pancreatic islets comprising only 1%-2% of the volume are highly vascularized and innervated mini-organs. They contain five endocrine cell types, including β cells that secrete insulin, which is synthesized as a single polypeptide chain, preproinsulin, processed to proinsulin, and finally to insulin and C-peptide. This process is complex and regulated, involving the Golgi complex, the endoplasmic reticulum, and the secretory granules of the β cell.
Insulin and C-peptide are...
Insulin and C-peptide are...
1.3K
T Cell Types and Functions
1.0K
When T cells with CD4 markers are activated, they give rise to two types of effector cells: helper T cells and regulatory T cells. Meanwhile, T cells with CD8 markers differentiate into effector cytotoxic T cells. The differentiation of CD4 T cells into helper T cell subsets, such as Th1, Th2, and Th17 cells, is dependent on the antigen type, antigen-presenting cell, and regulatory cytokines.
Th1 cells stimulate dendritic cells to express necessary co-stimulatory molecules on their surfaces for...
Th1 cells stimulate dendritic cells to express necessary co-stimulatory molecules on their surfaces for...
1.0K
Glucagon-like Receptor Agonists
321
Incretins include glucagon-like peptide-1 (GLP-1) and glucose-dependent insulinotropic polypeptide (GIP), which stimulate insulin secretion post-meals. In type 2 diabetes, GIP's efficacy is reduced, making GLP-1 a viable drug target. GIP originates from preproGIP.
GLP-1, when administered in high doses intravenously, triggers insulin secretion, inhibits glucagon release, slows gastric emptying, reduces food intake, and restores normal insulin secretion. However, its rapid inactivation by...
GLP-1, when administered in high doses intravenously, triggers insulin secretion, inhibits glucagon release, slows gastric emptying, reduces food intake, and restores normal insulin secretion. However, its rapid inactivation by...
321


