在炎症期间调节巨细胞活动的HMGB1依赖信号
Justyna Agier1, Sylwia Różalska2, Magdalena Wiktorska3
1Department of Microbiology, Genetics and Experimental Immunology, Centre of Molecular Studies on Civilization Diseases MOLecoLAB, Medical University of Lodz, Lodz, Poland.
Frontiers in immunology
|October 20, 2025
概括
高流动性组盒子1 (HMGB1) 蛋白质通过增加模式识别受体 (PRR) 表达和媒介释放来增强乳腺细胞 (MC) 活性和炎症反应. 这突出了HMGB1作为炎症疾病的治疗点.
科学领域:
- 免疫学 免疫学 免疫学
- 细胞生物学 细胞生物学
- 分子生物学分子生物学
背景情况:
- 损坏的细胞会释放像HMGB1这样的警示蛋白,以发出危险信号并启动炎症.
- 乳腺细胞 (MCs) 在炎症中起着关键作用,并可能感知到细胞损伤.
- HMGB1与高级糖化最终产品受体 (RAGE) 相互作用,以信号受损的平衡.
研究的目的:
- 调查HMGB1是否影响成熟的MCs中的模式识别受体 (PRR) 表达.
- 为了确定HMGB1是否调节MC炎症反应,包括介质的产生和迁移.
- 探索RAGE和信号通路在HMGB1-介导的MC激活中的作用.
主要方法:
- 实验使用成熟的老鼠MCs从腹腔中分离出来.
- 评估了HMGB1对MC PRR表达,介质生成/释放和迁移的影响.
主要成果:
- 在MC中,HMGB1显著增加了Dectin-1,RIG-I和NOD1的表达.
- HMGB1刺激了MCs产生CCL3,IL-1β,TNF,cysLTs,基因组胺和ROS.
- HMGB1充当了MCs的化学吸引剂,RAGE抗剂减弱了反应.
- 由HMGB1诱导的MC激活涉及ERK1/2,p38 MAPK,PI3K,NF-κB和JAK2.2等信号通路.
结论:
- HMGB1是一种关键的内源性警报蛋白,增强了MC活性和炎症过程.
- HMGB1成为管理MC驱动的炎症状况的潜在治疗标.
- 这些发现支持MCs作为细胞损伤的关键传感器,对像HMGB1.1这样的警示蛋白做出反应.
相关概念视频
Inflammation
61.6K
Overview
61.6K
Antiasthma Drugs: Mast Cell Stabilizers and Anti-IgE Drugs
1.7K
Asthma is a chronic respiratory condition for which new therapeutic avenues, including anti-inflammatory drugs like mast cell stabilizers and anti-IgE treatments, continue to be developed.
Mast cell stabilizers, such as cromolyn (also known as sodium cromoglycate) and nedocromil (Tilade), are effective drugs in asthma management. These stabilizers hinder histamine release by skillfully obstructing the activation of mast cells and other cellular entities. Notably, they navigate this task without...
Mast cell stabilizers, such as cromolyn (also known as sodium cromoglycate) and nedocromil (Tilade), are effective drugs in asthma management. These stabilizers hinder histamine release by skillfully obstructing the activation of mast cells and other cellular entities. Notably, they navigate this task without...
1.7K
Activation and Inactivation of G Proteins
10.9K
Heterotrimeric G proteins are guanine nucleotide-binding proteins. As the name suggests, heterotrimeric G proteins are composed of three subunits: alpha, beta, and gamma. They remain GDP-bound or GTP-bound inside the cells and switch between inactive/active states. The Gα subunit possesses the nucleotide-binding pocket that binds guanine nucleotides and switches between GDP or GTP-bound states. In contrast, the Gꞵ and Gγ subunits are always bound together with high...
10.9K
Differentiation of Common Myeloid Progenitor Cells
3.9K
Common myeloid progenitors (CMPs) are oligopotent cells that can differentiate into granulocytes and macrophages. Granulocytes and macrophages are essential for protecting the body against bacterial, viral, or fungal infections. They migrate from the bone marrow into the circulating blood to reach specific tissue sites where they differentiate and help in immune surveillance. However, they survive only for a few days and must be continuously made available to the organism to maintain a robust...
3.9K
GPCRs Regulate Adenylyl Cylase Activity
7.3K
Some GPCRs transmit signals through adenylyl cyclase (AC), a transmembrane enzyme. AC helps synthesize second messenger cyclic adenosine monophosphate (cAMP). AC catalyzes cyclization reaction and converts ATP to cAMP by releasing a pyrophosphate. The pyrophosphate is further hydrolyzed to phosphate by the enzyme pyrophosphatase, which drives cAMP synthesis to completion. However, cAMP is rapidly degraded to 5′ AMP by the enzymes phosphodiesterase (PDE), preventing overstimulation of...
7.3K
IP3/DAG Signaling Pathway
14.2K
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...
14.2K


