卡斯帕斯-6 是先天免疫,炎症细胞激活和宿主防御的关键调节剂
Min Zheng1, Rajendra Karki1, Peter Vogel2
1Department of Immunology, St. Jude Children's Research Hospital, Memphis, TN 38105, USA.
Cell
|April 17, 2020
概括
卡斯巴酶对抗流感A病毒的先天免疫和宿主防御至关重要. 它激活了炎细胞和编程细胞死亡途径, 为疾病提供了新的治疗点.
科学领域:
- 免疫学
- 细胞生物学
- 病毒学
背景情况:
- 体是细胞死亡和免疫反应的关键调节者.
- 一种子酶,除了亡之外,其功能还不太清楚.
- 它在先天免疫力和炎症酶激活中的特定作用在很大程度上尚未被探索.
研究的目的:
- 研究caspase-6在先天免疫和炎症酶激活中的作用.
- 确定caspase-6在编程细胞死亡途径和宿主抗流感A病毒 (IAV) 的参与.
- 阐明Z-DNA结合蛋白1 (ZBP1) 中介信号中的酶-6的机制.
主要方法:
- 研究了酶-6在炎症酶激活和编程细胞死亡中的作用 (pyroptosis,apoptosis,necroptosis - PANoptosis).
- 在流感A病毒感染期间评估caspase-6在宿主防御中的功能.
- 研究了卡斯帕斯-6对替代激活巨细胞 (AAM) 差异化的作用.
- 在RIP同型相互作用动机 (RHIM) 依存复合体形成中分析了caspase-6,RIPK3和ZBP1之间的相互作用.
主要成果:
- 卡斯巴酶-6调解先天免疫和炎症酶激活.
- 卡斯巴促进了PANoptosis,对抗甲型流感病毒 (IAV) 的宿主防御至关重要.
- 通过RIPK3促进RIPK3- ZBP1结合,这对于ZBP1介导的炎症酶激活至关重要.
- 卡斯帕斯-6促进替代激活的巨细胞分化.
结论:
- 在IAV感染期间,卡斯巴酶-6在ZBP1介导的炎症酶激活,细胞死亡和宿主防御中发挥着至关重要的作用.
- 这些发现突出显示caspase-6是传染病,自身炎症和癌症的潜在治疗点.
- 卡斯巴酶6的功能超越了细胞亡,包括免疫和细胞死亡调节中的关键作用.
相关概念视频
Caspases
13.5K
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...
13.5K
The Extrinsic Apoptotic Pathway
7.8K
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...
7.8K
The Intrinsic Apoptotic Pathway
8.0K
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...
8.0K
NF-κB-dependent Signaling Pathway
9.7K
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...
9.7K
Inflammatory Response
15.6K
An inflammatory response is a localized, nonspecific immune reaction that occurs when a tissue is injured. It is characterized by redness, swelling, heat, and pain, which are commonly called the cardinal signs and symptoms of inflammation. Inflammation can sometimes result in a loss of function.
Inflammation can be triggered by various stimuli, such as impact, abrasion, chemical irritation, infections, and extreme hot or cold temperatures. These can damage cells and connective tissue fibers,...
Inflammation can be triggered by various stimuli, such as impact, abrasion, chemical irritation, infections, and extreme hot or cold temperatures. These can damage cells and connective tissue fibers,...
15.6K
CRISPR and crRNAs
18.5K
Bacteria and archaea are susceptible to viral infections just like eukaryotes; therefore, they have developed a unique adaptive immune system to protect themselves. Clustered regularly interspaced short palindromic repeats and CRISPR-associated proteins (CRISPR-Cas) are present in more than 45% of known bacteria and 90% of known archaea.
The CRISPR-Cas system stores a copy of foreign DNA in the host genome and uses it to identify the foreign DNA upon reinfection. CRISPR-Cas has three different...
The CRISPR-Cas system stores a copy of foreign DNA in the host genome and uses it to identify the foreign DNA upon reinfection. CRISPR-Cas has three different...
18.5K


