相关实验视频
Updated: Jun 23, 2025

07:37
An Adoptive Transfer Model of Rheumatoid Arthritis in Mice
Published on: June 6, 2025
68
塞拉斯特调节Hsp90-NLRP3相互作用以缓解类风湿性关节炎
Junjie Yang1, Biyao He1, Longjiao Dang1
1Key Laboratory of Prescription Effect and Clinical Evaluation of State Administration of Traditional Chinese Medicine of China, School of Pharmacy, Binzhou Medical University, Yantai, 264003, China.
Inflammation
|June 14, 2024
概括
塞拉斯 (Cel) 通过抑制NLRP3炎症酶来治疗类风湿性关节炎. 它通过阻断纤维细胞样同胞细胞中的Hsp90和NLRP3相互作用而起作用,减少炎症和疾病严重程度.
科学领域:
- 免疫学 免疫学 免疫学
- 药理学 药理学是指药理学的学科.
- 分子生物学分子生物学
背景情况:
- 类风湿性关节炎 (RA) 是一种自身免疫性疾病,其特征是关节炎症.
- 塞拉斯特 (Cel) 通过抑制NLRP3炎症酶,显示出对RA的保护作用.
- 塞尔对NLRP3的作用的精确分子机制尚不清楚.
研究的目的:
- 阐明塞拉斯特 (Cel) 调节类型为类风湿性关节炎 (RA) 的NLRP3炎症酶通路的特定分子机制.
- 调查Cel. 的体外和体内抗关节炎作用.
- 确定Cel与Hsp90的相互作用及其对Hsp90-NLRP3复合体的影响.
主要方法:
- 一种原诱导性关节炎 (CIA) 鼠标模型被用于评估Cel的抗关节炎活性,包括爪子胀,关节炎得分和组织病理学.
- 在体外研究包括评估Cel对TNF-α诱导的纤维细胞样同胞细胞 (FLS) 的影响,包括增殖,迁移和益炎性细胞因子产生 (ELISA).
- 研究分子机制使用西式涂抹,免疫光染色,分子对接,Octet RED96系统和共免疫沉来分析NF-κB/NLRP3途径组件和Cel-Hsp90相互作用.
主要成果:
- 在CIA小鼠模型中,塞拉斯特显著降低了关节炎的严重程度.
- 塞尔证明了对TNF-α诱导的FLS的抗增殖和抗迁移作用.
- 塞尔抑制了NF-κB/NLRP3信号通路的激活,减少了活性氧物种 (ROS) 的产生,并抑制了促炎性细胞因子分泌.
- 塞尔直接与Hsp90结合,并破坏了FLS中的Hsp90-NLRP3相互作用.
结论:
- 塞拉斯特有效调节NLRP3炎症体信号通路,无论是体内还是体外.
- 在RA中Cel的治疗效果通过抑制FLS的扩散和迁移来介导.
- 塞尔通过阻止Hsp90和NLRP3之间的相互作用来实现这一目标,从而调节NLRP3炎症酶途径.
相关概念视频
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
T Cell Types and Functions
999
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...
999
Regulation of the Unfolded Protein Response
2.4K
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...
2.4K
Drugs for Treatment of Crohn's Disease in IBD Using Immunomodulatory Agents
156
Crohn's disease is an inflammatory bowel disorder marked by chronic inflammation of the GI tract. Various treatment strategies for Crohn's disease are employed, such as immunomodulatory agents, glucocorticoids, and biologics or anti-TNF therapy. Azathioprine (Imuran), a commonly used immunomodulatory drug for Crohn's disease, is converted in the body to mercaptopurine, which inhibits purine biosynthesis and cell proliferation. Both are utilized in severe cases of Inflammatory Bowel...
156
Drugs for Treatment of Crohn's Disease in IBD Using Biologic Agents: Anti-TNF
130
Tumor Necrosis Factor (TNF), a proinflammatory cytokine, contributes significantly to the inflammation seen in Crohn's disease. It exists as soluble TNF and membrane-bound TNF, with actions mediated through TNF receptors (TNFR). TNFR activation leads to the release of proinflammatory cytokines, T-cell activation, collagen production, and leukocyte migration, all contributing to inflammation in Crohn's disease. Anti-TNF monoclonal antibodies, namely infliximab (Remicade), adalimumab...
130

