Cirsii Herba糖蛋白通过与TLR4相互作用,通过MAPK和NF-κB信号通路促进巨细胞M1两极分化
Ming Zhao1, Shiyue Qin1, Jiaqi Wang1
1MOA Key Laboratory of Animal Virology, Center for Veterinary Sciences, Department of Veterinary Medicine, College of Animal Sciences, Zhejiang University, Hangzhou 310058, China.
International journal of biological macromolecules
|January 10, 2025
概括
草糖蛋白 (CHP) 激活巨细胞,增强免疫反应. 它们通过依赖于托尔类受体4 (TLR4) 的MAPK和NF-κB通路促进M1极化.
科学领域:
- 免疫学 免疫学 免疫学
- 生物化学 生化学
- 药理学 药理学是指药理学的学科.
背景情况:
- 传统上使用Cirsii Herba (CHP),但其免疫调节作用需要详细研究.
- 了解免疫细胞中CHP的分子机制对于治疗应用至关重要.
研究的目的:
- 从Cirsii Herba (CHPs) 中提取和表征糖蛋白.
- 研究RAW264.7巨细胞中CHP的免疫调节活性和分子机制.
- 阐明参与CHP诱导的巨细胞激活的信号通路.
主要方法:
- 从Cirsii Herba中提取和净化糖蛋白.
- 生物化学表征CHP (蛋白质,碳水化合物,氨基酸,单糖化合物组成).
- 评估巨细胞的功能 (皮诺细胞,细胞,炎症因子分泌).
- 使用RNA测序 (RNA-seq),基因本体学 (GO),KEGG通路分析和通路抑制试验分析分子机制.
- 使用受体阻断或抑制试验识别功能性受体.
主要成果:
- CHP被确定为富含蛋白质 (80.4%) 和碳水化合物 (14.8%) 的~70kDa糖蛋白,具有特定的氨基酸和单糖样.
- CHP显著增强了巨细胞的皮诺细胞和细胞活动.
- 慢性肝炎增加了炎症因子 (NO,TNF-α,IL-6) 和化学激素 (CXCL2,CXCL10) 的分泌,并上调了辅助/辅助刺激分子 (CD40,CD80,CD86,MHC I/II).
- RNA-seq揭示了基因表达的显著变化,MAPK和NF-κB信号通路的丰富.
- 收费类受体4 (TLR4) 被确定为参与CHP识别和随后的巨细胞激活的关键受体.
结论:
- 慢性增生细胞具有显著的免疫调节活性,增强巨细胞功能和炎症反应.
- 合并疗法的免疫调节作用是通过TLR4依赖的MAPK和NF-κB信号通路的激活来实现的.
- CHP促进了对M1表型的巨细胞两极分化,这表明在免疫调节中具有潜在的治疗应用.
相关概念视频
NF-κB-dependent Signaling Pathway
7.2K
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...
7.2K
IP3/DAG Signaling Pathway
11.9K
Membrane lipids such as phosphatidylinositol (PI) are precursors for several membrane-bound and soluble second messengers. Specific kinases phosphorylate PI and produce phosphorylated inositol phospholipids. One such inositol phospholipids are the phosphatidylinositol-4,5 bisphosphate [PI(4,5)P2], present in the inner half of the lipid bilayer. Upon ligand binding, GPCR stimulates Gq proteins to turn on phospholipase Cꞵ. Activated phospholipase Cꞵ cleaves PI(4,5)P2 and...
11.9K
Receptor Downregulation in MVBs
2.0K
Multivesicular bodies (MVBs) are mature endosomes that sort ubiquitinated proteins and then fuse with lysosomes to degrade the sorted proteins. Epidermal growth factor (EGF) and its receptor (EGFR) form a complex that can be internalized through endocytosis, sorted into an MVB, and later degraded.
The EGFR can initiate signaling pathways that lead to cell proliferation, migration, and differentiation. Overexpression of EGFR stimulates cells to proliferate. Excessive EGFR...
The EGFR can initiate signaling pathways that lead to cell proliferation, migration, and differentiation. Overexpression of EGFR stimulates cells to proliferate. Excessive EGFR...
2.0K
Interactions Between Signaling Pathways
6.2K
Signaling cascades usually lack linearity. Multiple pathways interact and regulate one another, allowing cells to integrate and respond to diverse environmental stimuli.
Convergence and divergence, and cross-talk between signaling pathways
Two distinct signaling pathways can converge on a single functional unit, which may either be a single protein or a complex of proteins. The response is either functionally distinct or synergistic between the two pathways but different from the response...
Convergence and divergence, and cross-talk between signaling pathways
Two distinct signaling pathways can converge on a single functional unit, which may either be a single protein or a complex of proteins. The response is either functionally distinct or synergistic between the two pathways but different from the response...
6.2K
MAPK Signaling Cascades
5.2K
Mitogen-activated protein kinase, or MAPK pathway, activates three sequential kinases to regulate cellular responses such as proliferation, differentiation, survival, and apoptosis. The canonical MAPK pathway starts with a mitogen or growth factor binding to an RTK. The activated RTKs stimulate Ras, which recruits Raf or MAP3 Kinase (MAPKKK), the first kinase of the MAPK signaling cascade. Raf further phosphorylates and activates MEK or MAP2 Kinases (MAPKK), which in turn phosphorylates MAP...
5.2K


