卡瑟普辛C抑制降低中性粒细胞血清蛋白酶活性,并改善激活中性粒细胞介导疾病
Yuka Nishibata1, Suishin Arai1, Mai Taniguchi1
1Department of Medical Laboratory Science, Faculty of Health Sciences, Hokkaido University, Sapporo, Japan.
Nature communications
|August 22, 2024
概括
素C (CatC) 抑制剂,如MOD06051,可以减少中性粒细胞的激活和中性粒细胞外细胞陷 (NET) 的形成. 这表明,CatC抑制对于由中性粒细胞驱动的炎症性疾病是一种有前途的治疗策略.
科学领域:
- 免疫学 免疫学 免疫学
- 生物化学 生物化学
- 药理学 药理学是指药理学的学科.
背景情况:
- 甲素C (CatC) 调节中性粒细胞血清蛋白酶 (NSP),对中性粒细胞激活至关重要.
- 活性中性粒细胞和中性粒细胞外细胞陷 (NETs) 与炎症性疾病有关.
研究的目的:
- 评估CatC抑制剂在涉及NET的疾病中的治疗潜力.
- 研究CatC抑制对中性粒细胞激活和NET形成的影响.
主要方法:
- 在体外评估CatC抑制剂MOD06051对NSP活性,包括中性粒细胞弹性酶 (NE).
- 对接受MOD06051.1治疗的老鼠中性粒细胞中NE活性和NET形成的评估.
- 将MOD06051给肌氧化酶 (MPO) - 抗核素细胞质抗体相关血管炎 (AAV) 的老鼠模型,以评估治疗效果.
主要成果:
- MOD06051在体外以剂量为依赖的方式抑制了NSP活性.
- 接受MOD06051治疗的老鼠的中性粒细胞显示NE活性降低和NET形成.
- 在MPO-AAV.的小鼠模型中,MOD06051改善了血管炎和降低了NETs.
结论:
- 素C的抑制有效地减少了中性粒细胞的激活和NET的形成.
- MOD06051证明了对MPO-AAV.等炎症状况的治疗潜力.
- 向CatC提供了一个有希望的策略来管理中性粒细胞介导疾病.
更多相关视频
11:32Real-Time, High-Throughput Microscopic Quantification of Human Neutrophil Extracellular Trap Release and Assessing the Pharmacology of Antagonists
Published on: October 18, 2024
568
19:16The Importance of Correct Protein Concentration for Kinetics and Affinity Determination in Structure-function Analysis
Published on: March 17, 2010
20.6K
相关概念视频
01:24Caspases
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
02:18The Proteasome
8.6K
Eukaryotic cells can degrade proteins through several pathways. One of the most important amongst these is the ubiquitin-proteasome pathway. It helps the cell eliminate the misfolded, damaged, or unwarranted cytoplasmic proteins in a highly specific manner.
In this pathway, the target proteins are first tagged with small proteins called ubiquitin. A series of enzymes carry out the ubiquitination of the target proteins - E1 (ubiquitin-activating enzyme), E2 (ubiquitin-conjugating enzyme), and E3...
In this pathway, the target proteins are first tagged with small proteins called ubiquitin. A series of enzymes carry out the ubiquitination of the target proteins - E1 (ubiquitin-activating enzyme), E2 (ubiquitin-conjugating enzyme), and E3...
8.6K