可转化阻断NF-κB/IκBα通路通过针对性涂层IκBα对抗类风湿性关节炎
Linhong Liu1, Mengru Ding2, Miaomiao Zheng3
1CAS Key Laboratory for the Biological Effects of Nanomaterials and Nanosafety, Institute of High Energy Physics, Chinese Academy of Sciences, Beijing, 100049, PR China; College of Chemistry and Life Science, Beijing University of Technology, Beijing, 100124, PR China.
Biomaterials
|September 17, 2024
概括
一种新可以转化为纳米颗粒,用于治疗类风湿性关节炎 (RA). 这种可以阻断关键的炎症通路,减少关节胀和组织破坏,在老鼠模型中,为自身免疫性疾病提供了新的治疗策略.
科学领域:
- 生物医学工程 生物医学工程
- 免疫学 免疫学 免疫学
- 纳米技术 纳米技术
背景情况:
- 类风湿性关节炎 (RA) 是一种复杂的自身免疫性疾病,具有破坏性影响.
- 目前针对单个炎症性细胞因子的治疗方法通常不足,这是由于RA的多面性病原性.
- 需要新的治疗策略来有效地管理RA进展.
研究的目的:
- 开发和评估用于治疗类风湿性关节炎的智能可转化 (BFD).
- 研究BFD的自我组装,细胞吸收和免疫细胞中的作用机制.
- 评估BFD在已建立的原诱导关节炎 (CIA) 鼠标模型中的治疗疗效.
主要方法:
- 开发一种可转化 (BP-FFVLK-DSGLDSM,BFD),能够自组装成纳米粒子.
- 研究BFD与免疫细胞内的IκBα酸化部位的相互作用.
- 评估BFD抑制NF-κB信号传递和减少促炎介质的能力.
- 评估BFD在原诱导性关节炎 (CIA) 鼠标模型中的疗效,测量关节胀,组织损伤和骨/软骨破坏.
主要成果:
- BFD自组装成纳米粒子,以提高交付和分发.
- BFD有效地向和转化免疫细胞内部,阻断IκBα酸化和NF-κB激活.
- 在CIA老鼠模型中,BFD显著缓解了关节炎的表现,包括关节胀和骨/软骨破坏.
- 治疗结果与BFD的生物分布,IκBα抑制和炎症性细胞因子的减少相关.
结论:
- 可转化BFD证明了对类风湿性关节炎的显著治疗潜力.
- 通过向关键的细胞内信号通路,BFD独特的作用机制为管理炎症疾病提供了一种新的方法.
- 这项研究强调了智能基纳米材料在自身免疫性疾病治疗中的前景.
相关概念视频
NF-κB-dependent Signaling Pathway
7.3K
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...
7.3K
Drugs for Treatment of Crohn's Disease in IBD Using Biologic Agents: Anti-TNF
119
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...
119
TGF - β Signaling Pathway
7.3K
The TGF-β signaling pathway regulates cell growth, differentiation, adhesion, motility, and development. TGF-β ligands that induce TGF-β signaling are synthesized in their latent form. Several proteases or cell surface receptors such as integrins act upon the latent form, releasing the active ligand. There are three types of mammalian TGF-βs: (TGF-β1, TGF-β2, and TGF-β3) that bind as homodimers or heterodimers to TGF-β receptors. The TGF-β receptors...
7.3K
T Cell Types and Functions
960
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...
960
The JAK-STAT Signaling Pathway
8.7K
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...
8.7K
Drugs for Treatment of Crohn's Disease in IBD Using Immunomodulatory Agents
145
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...
145


