伊塔科纳酸减少纤维细胞样同胞细胞的增殖和迁移,并改善关节炎模型
Maria Tada1, Yuki Kudo1, Michihito Kono1
1Department of Rheumatology, Endocrinology and Nephrology, Faculty of Medicine and Graduate School of Medicine, Hokkaido University, Sapporo, Japan.
Clinical immunology (Orlando, Fla.)
|May 19, 2024
概括
伊塔科纳酸 (ITA) 通过抑制纤维细胞样同胞细胞 (FLS) 的增殖和迁移来减少类风湿性关节炎 (RA). 这种代谢物显示了RA治疗的治疗潜力.
科学领域:
- 生物化学 生物化学
- 免疫学 免疫学 免疫学
- 代谢学 代谢学 代谢学
背景情况:
- 纤维细胞样同胞细胞 (FLS) 是类风湿性关节炎 (RA) 发病过程中的关键参与者.
- 伊塔康酸 (ITA) 是三碳酸 (TCA) 循环中的一种代谢物,具有抗炎性质.
研究的目的:
- 调查ITA对FLS的影响.
- 评估ITA在治疗RA方面的治疗潜力.
主要方法:
- 在体外测试中评估了FLS的扩散和迁移.
- 细胞外流量分析测量了线粒体的氧化酸化和糖解.
- 使用了大鼠和小鼠的II型原抗体诱导性关节炎 (CIA) 和原抗体诱导性关节炎 (CAIA) 模型.
- 使用缺少Irg1的小鼠来研究ITA的内生作用.
主要成果:
- 在实验室中,ITA显著抑制了FLS的扩散和迁移.
- 在FLS中,ITA降低了线粒体的氧化酸化和糖解.
- 在CIA的老鼠模型中,ITA治疗改善了关节炎和骨质侵蚀.
- 在CAIA模型中,缺乏ITA生产 (Irg1缺乏) 的小鼠表现出恶化的关节炎.
结论:
- 通过针对FLS,ITA显示出显著的抗关节炎作用.
- ITA可以作为一种新的治疗剂,用于类风湿性关节炎.
相关概念视频
Drugs for Treatment of Crohn's Disease in IBD Using Biologic Agents: Anti-TNF
131
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...
131
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
1.0K
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...
1.0K
Drugs for Treatment of Crohn's Disease in IBD Using Immunomodulatory Agents
158
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...
158
Intracellular Signaling Affects Focal Adhesions
2.7K
Integrins act both as extracellular input receivers and as intracellular processing activators. As their name suggests, integrins are entirely integrated into the membrane structure. Their hydrophobic membrane-spanning regions interact with the phospholipid bilayer's hydrophobic region. These membrane receptors provide extracellular attachment sites for effectors like hormones and growth factors. They activate intracellular response cascades when their effectors are bound and active.
Some...
Some...
2.7K


