DDX6通过NF-κB激活参与炎症性疾病的发病
Seiichiro Naito1, Hiroki Tanaka2, Jing-Jing Jiang2
1Division of Molecular Psychoimmunology, Institute for Genetic Medicine, Graduate School of Medicine, Hokkaido University, Sapporo, Japan; Department of Cardiovascular Medicine, Graduate School of Medicine, Hokkaido University, Sapporo, Japan.
Biochemical and biophysical research communications
|February 20, 2024
概括
死亡盒酶6 (DDX6) 调节IL-6放大器通路,在慢性炎症中至关重要. 沉默DDX6抑制NF-κB激活和炎症疾病模型,表明DDX6作为治疗点.
科学领域:
- 免疫学 免疫学 免疫学
- 分子生物学分子生物学
- 细胞生物学 细胞生物学
背景情况:
- 介素-6 (IL-6) 放大器通路增强了非免疫细胞中核因子kappa B (NF-κB) 的激活.
- 这一途径导致IL-6和生长因子的过度产生,促进慢性炎症和炎症性疾病.
研究的目的:
- 通过IL-6放大器,研究DEAD-Box Helicase 6 (DDX6) 在炎症性疾病的发病过程中的作用.
- 阐明DDX6影响NF-κB信号传输和IL-6放大器的机制.
主要方法:
- 利用shRNA介导的全基因组查来确定DDX6作为潜在的调节者.
- 在非免疫细胞中进行DDX6沉默和强制表达实验.
- 研究了DDX6对NF-κB促进体活性和关键信号分子 (p65/RelA,IκBα) 的影响.
- 采用一只因伊米基莫德诱导的皮肤炎小鼠模型来评估DDX6在体内发挥的作用.
主要成果:
- 抑制DDX6抑制了NF-κB通路,并抑制了IL-6放大器的激活.
- 强迫DDX6表达增强了NF-κB促进体活性,独立于其RNA酶功能.
- 降低DDX6的调节改善了因伊米基莫德介导的皮肤炎.
- 沉默DDX6降低了TNF-α诱导的p65/RelA和IkBα酸化,p65核定位和IkBα蛋白水平.
- 发现DDX6与p65和IκBα结合在一起,这表明NF-κB通路中的适应蛋白功能.
结论:
- DDX6在调节IL-6放大器和NF-κB通路激活方面发挥着重要作用.
- DDX6的功能超出了RNA代谢,作为NF-κB信号传递中的适应蛋白.
- 在炎症性疾病中,DDX6是潜在的治疗点.
相关概念视频
NF-κB-dependent Signaling Pathway
7.4K
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...
7.4K
Co-activators and Co-repressors
7.4K
Gene transcription is regulated by the synergistic action of several proteins that form a complex at a gene regulatory site. This is observed in eukaryotes, where the regulation of gene expression is a complex process. Regulatory proteins in eukaryotes can broadly be classified into two types – regulators that bind directly to specific DNA sequences and co-regulators that associate with regulatory proteins but cannot directly bind to the DNA. These co-regulators are further divided into...
7.4K
The JAK-STAT Signaling Pathway
8.9K
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...
8.9K
Drugs for Treatment of Crohn's Disease in IBD Using Biologic Agents: Anti-TNF
137
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...
137
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
The Extrinsic Apoptotic Pathway
6.4K
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...
6.4K


