ANGPTL3通过抑制IL1R1相关的信号复合组件组合来负面调节IL-1β诱导的NF-κB激活
Yu Zhang1, Zi-Tong Zhang1, Shi-Yuan Wan1
1Tongji School of Pharmacy, Tongji Medical College and State Key Laboratory for Diagnosis and Treatment of Severe Zoonotic Infectious Diseases, Huazhong University of Science and Technology, Wuhan 430030, China.
Journal of molecular cell biology
|August 27, 2023
概括
细胞内类似3的 ангиопоетин (ANGPTL3) 通过防止IL-1R1 (IL1R1) 和IL-1R辅助蛋白 (IL1RAP) 之间的相互作用来抑制炎症,维持免疫平衡.
科学领域:
- 免疫学 免疫学 免疫学
- 分子生物学分子生物学
- 肝病学 肝病学是一种肝病学.
背景情况:
- 干白素-1β (IL-1β) 信号传递对炎症和免疫至关重要,由IL-1受体1型 (IL1R1) 和IL-1R辅助蛋白 (IL1RAP) 综合体启动.
- 类似3的angiopoietin (ANGPTL3) 已知可以调节脂质代谢,但其细胞内功能,特别是免疫功能,在很大程度上尚未被探索.
研究的目的:
- 为了研究像3的angiopoietin (ANGPTL3) 在调节interleukin-1β (IL-1β) 诱导的炎症信号中的细胞内作用.
- 阐明ANGPTL3调节IL-1β受体复合组件的机制.
主要方法:
- 使用的细胞系 (HepG2,THP1,HEK293T) 具有ANGPTL3过度表达,淘汰或淘汰.
- 进行共免疫沉试验以评估蛋白质相互作用.
- 测量NF-κB激活和炎症基因转录.
主要成果:
- 细胞内ANGPTL3的过度表达抑制了IL-1β诱导的NF-κB激活和炎症基因表达.
- 抑制或淘汰ANGPTL3增强的IL-1β信号传递.
- ANGPTL3直接与IL1R1和IL1RAP相互作用,通过其C端纤维素原样域破坏了它们的复杂组合.
结论:
- 细胞内 ANGPTL3 作为 IL-1β 触发炎症的新型负调节剂.
- ANGPTL3通过抑制IL1R1-IL1RAP复合体的形成来维持免疫耐受性和肝脏平衡.
相关概念视频
NF-κB-dependent Signaling Pathway
7.5K
The transcription factor NF-κB was discovered in 1986 in the lab of Nobel laureate Professor David Baltimore, for its interaction with the immunoglobulin light chain enhancer in B-cells. After more than three decades of study, it is now evident that NF-κB regulates the expression of over 100 genes. Most of these genes play an essential role in the innate and adaptive immune responses as well as the inflammatory responses of animals.
NF-κB-dependent Signaling Mechanism
The...
NF-κB-dependent Signaling Mechanism
The...
7.5K
TGF - β Signaling Pathway
7.4K
The TGF-β signaling pathway regulates cell growth, differentiation, adhesion, motility, and development. TGF-β ligands that induce TGF-β signaling are synthesized in their latent form. Several proteases or cell surface receptors such as integrins act upon the latent form, releasing the active ligand. There are three types of mammalian TGF-βs: (TGF-β1, TGF-β2, and TGF-β3) that bind as homodimers or heterodimers to TGF-β receptors. The TGF-β receptors...
7.4K
T Cell Types and Functions
1.1K
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...
1.1K
The JAK-STAT Signaling Pathway
9.0K
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...
9.0K
PI3K/mTOR/AKT Signaling Pathway
3.6K
The mammalian target of rapamycin (mTOR) is a serine/threonine kinase that regulates growth, proliferation, and cell survival in response to hormones, growth factors, or nutrient availability. This kinase exists in two structurally and functionally distinct forms: mTOR complex 1 (mTORC1) and mTOR complex 2 (mTORC2). The first form (mTORC1) is composed of a rapamycin-sensitive Raptor and proline-rich Akt substrate, PRAS40. In contrast, mTORC2 consists of a...
3.6K
Regulation of the Unfolded Protein Response
2.5K
Inositol-requiring kinase one or IRE1 is the most conserved eukaryotic unfolded protein response (UPR) receptor. It is a type I transmembrane protein kinase receptor with a distinctive site-specific RNase activity. As the binding mechanics of the misfolded proteins with the N-terminal domain of IRE-1 are unclear, three binding models — direct, indirect, and allosteric -- are proposed for receptor activation. Nevertheless, it is known that once a misfolded protein associates with IRE1, it...
2.5K


