C4b结合蛋白抑制颗粒物和晶体诱导的NLRP3炎症酶激活
Damien Bierschenk1, Nikolina Papac-Milicevic2, Ian P Bresch3,4
1Division of Medical Protein Chemistry, Department of Translational Medicine, Lund University, Malmö, Sweden.
Frontiers in immunology
|June 7, 2023
概括
C4b结合蛋白 (C4BP) 抑制了人体细胞中的晶体和颗粒对NLRP3炎症酶的激活. 此外,C4BP还可以保护小鼠免受炎症,维持组织平衡.
科学领域:
- 免疫学 免疫学 免疫学
- 分子生物学分子生物学
- 补充系统 补充系统
背景情况:
- NLRP3炎症酶失调与许多疾病有关.
- 对NLRP3炎症酶途径的内源性抑制剂尚不清楚.
- C4b结合蛋白 (C4BP) 是一种已知的补充抑制剂,在NLRP3炎症酶调节中发挥着新兴的作用.
研究的目的:
- 研究C4b结合蛋白 (C4BP) 作为NLRP3炎症酶激活的内源抑制剂.
- 确定C4BP抑制晶体和粒子诱导的炎症酶反应的机制.
- 评估C4BP的体内抗炎功能.
主要方法:
- 从人体血中净化C4BP.
- 在体外测试使用晶体 (单酸盐,MSU) 和颗粒 () 刺激.
- 使用突变组组对C4BP结合域的分析.
- 巨细胞内部化和炎症体复杂组装试验.
- 评估IL-1β分泌和溶酶体膜损伤.
- 在体内研究使用C4bp-/-小鼠挑战MSU.
主要成果:
- 纯化的C4BP抑制了人类巨细胞中MSU和二氧化诱导的NLRP3炎症酶激活.
- C4BP通过其α链上的特定域与MSU和颗粒结合.
- 内化C4BP降低了炎酶体复合体组合和IL-1β分泌.
- 保护C4BP免受MSU和二氧化引起的溶酶体膜损伤.
- C4bp-/-小鼠对MSU挑战表现出加剧的炎症反应.
结论:
- 内化C4BP作为一种内源性抑制剂,可以抑制水晶和粒子诱导的人类巨细胞中的炎症酶激活.
- 鼠C4BP在体内表现出具有保护性的抗炎作用.
- C4BP通过抑制颗粒刺激的炎症酶反应,在维持组织平衡中发挥着至关重要的作用.
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
The Intrinsic Apoptotic Pathway
6.6K
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...
6.6K
Complement System
2.5K
The complement system is a group of approximately 20 plasma proteins that strengthen the body's defenses against infections through opsonization, inflammation, and cell lysis. Opsonization involves coating pathogens with complement proteins, making them more recognizable and facilitating phagocyte engulfment. Certain complement proteins induce inflammation that attracts immune cells to the site of infection. Cell lysis involves the destruction of pathogens through the formation of a...
2.5K
GPCRs Regulate Adenylyl Cylase Activity
5.7K
Some GPCRs transmit signals through adenylyl cyclase (AC), a transmembrane enzyme. AC helps synthesize second messenger cyclic adenosine monophosphate (cAMP). AC catalyzes cyclization reaction and converts ATP to cAMP by releasing a pyrophosphate. The pyrophosphate is further hydrolyzed to phosphate by the enzyme pyrophosphatase, which drives cAMP synthesis to completion. However, cAMP is rapidly degraded to 5′ AMP by the enzymes phosphodiesterase (PDE), preventing overstimulation of...
5.7K
Caspases
12.6K
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...
12.6K


