卡斯帕斯-4/11促进高脂血症和慢性病加速血管炎症,通过增强训练免疫力来增强训练免疫力
1Lemole Center for Integrated Lymphatics and Vascular Research, Department of Cardiovascular Sciences, Lewis Katz School of Medicine at Temple University, Philadelphia, Pennsylvania, USA.
JCI insight
|July 18, 2024
概括
超脂血症和慢性病通过涉及caspase-11和IL-1B的双层训练免疫机制加速血管炎症. 这种协同作用促进了大动脉损伤和炎症反应.
科学领域:
- 心血管生物学 心血管生物学
- 免疫学 免疫学 免疫学
- 腎臟病學 (nephrology) 是一種醫學專業.
背景情况:
- 超脂血症和慢性病 (CKD) 是心血管疾病的危险因素.
- 血管炎症在动脉样硬化进展中起着关键作用.
- 训练免疫 (TI) 是一种天生的免疫记忆现象,可以导致慢性炎症.
研究的目的:
- 通过训练免疫来研究超脂血症和CKD对血管炎症的协同作用.
- 阐明这种协同效应背后的分子机制.
主要方法:
- 动脉病理分析和RNA测序在高脂肪饮食 (HFD) 5/6腎切除CKD (HFD+CKD) 的小鼠身上进行.
- 使用Caspase-11淘汰赛 (CASP11-/-) 小鼠来评估CASP11的作用.
- 进行了脂聚糖 (LPS) 转移到人类大动脉内皮细胞.
主要成果:
- HFD+CKD小鼠表现出大动脉细胞溶液LPS,caspase-11 (CASP11) 激活和TI通路基因表达的增加.
- CASP11缺乏减少了大动脉新密度增大,巨细胞招募和细胞因子分泌.
- 缺少CASP11会降低N端气体皮质D (N-GSDMD) 膜表达和IL-1B水平.
- 在人类大动脉内皮细胞中,LPS诱导了CASP4/CASP11激活和N-GSDMD表达.
- IL-1B被确定为HFD+CKD诱导的TI中的二级机制.
结论:
- 超脂血症和CKD通过双层训练免疫路径协同加速血管炎症.
- CASP11-GSDMD-IL-1B轴在调解HFD+CKD诱导的血管炎症和TI方面至关重要.
相关概念视频
Caspases
12.4K
Caspase, a family of cysteine proteases, serve as effectors in apoptosis. The ced3 gene in C.elegans was first identified to be involved in apoptosis. This gene encodes the ced-3 caspase that is similar to the interleukin-1-beta converting enzyme or ICE in mammals. In addition to apoptosis, caspases also function in the inflammatory response. Inflammatory caspases are essential in activating pro-inflammatory cytokines that recruit immune cells and block the replication of pathogens inside...
12.4K
The Extrinsic Apoptotic Pathway
6.3K
The extrinsic apoptotic pathway is initiated when extracellular death-inducing signals, such as specific cytokines, activate the death receptors expressed on the cell surface. The immune cells involved in this pathway are natural killer cells (NK cells) and cytotoxic T-lymphocytes. NK cells are critical in innate immune response, while cytotoxic T-lymphocytes are associated with adaptive immune response. These cells recognize specific receptors expressed on the altered cells and activate...
6.3K
Inflammation
53.3K
Overview
53.3K
The Intrinsic Apoptotic Pathway
6.5K
Internal cellular stress, such as cellular injury or hypoxia, triggers intrinsic apoptosis. The B-cell lymphoma 2 (Bcl-2) family of proteins are the primary regulators of the intrinsic apoptotic pathway. For example, during DNA damage, checkpoint proteins, such as Ataxia Telangiectasia Mutated (ATM protein) and Checkpoints Factor-2 (Chk2) proteins, are activated. These proteins phosphorylate p53 which further activates pro-apoptotic proteins, such as Bax, Bak, PUMA, and Noxa, and inhibits...
6.5K
The JAK-STAT Signaling Pathway
8.8K
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...
8.8K
Lipid-derived Compounds in the Human Body
4.3K
Fats and lipids are crucial components in the human body. Some lipid-derived compounds, such as fat-soluble vitamins, eicosanoids, lipoproteins, and glycolipids, also play unique roles to support various biological processes .
Fat-soluble Vitamins
Fat-soluble vitamins, including vitamins A, D, E, and K, are required in minimal quantities, but their deficiencies can lead to severely abnormal physiological conditions. For example, vitamin A deficiency can cause night blindness, dry skin,...
Fat-soluble Vitamins
Fat-soluble vitamins, including vitamins A, D, E, and K, are required in minimal quantities, but their deficiencies can lead to severely abnormal physiological conditions. For example, vitamin A deficiency can cause night blindness, dry skin,...
4.3K


