Ioannidis Melina, Tjepkema Johanna, Uitbeijerse Michael R P, van den Bogaart Geert
Department of Molecular Immunology, Groningen Biomolecular Science and Biotechnology Institute, University of Groningen, Nijenborgh 7, 9747AG, Groningen, the Netherlands.
Department of Molecular Immunology, Groningen Biomolecular Science and Biotechnology Institute, University of Groningen, Nijenborgh 7, 9747AG, Groningen, the Netherlands; Department of Medical Biology and Pathology, University Medical Centre Groningen, Groningen, the Netherlands.
Redox Biol. 2025 Jun 6;85:103719. doi: 10.1016/j.redox.2025.103719.
The reactive aldehyde 4-hydroxy-2-nonenal (4-HNE) is a byproduct of lipid peroxidation driven by reactive oxygen species (ROS). 4-HNE covalently binds to macromolecules such as proteins, altering their functions. While 4-HNE is implicated in various ROS-related pathologies, its impact on the immune system remains incompletely understood. This review explores how 4-HNE influences molecular mechanisms involved in inflammation and immune cell functions. 4-HNE modulates inflammation through the interaction with several signaling pathways, including nuclear factor kappa-light-chain enhancement of activated B cells (NF-κB), nuclear factor erythroid 2-related factor (Nrf2), mitogen-activated protein kinases (MAPK), toll-like receptor (TLR) 4, and stimulator of interferon genes (STING), thereby affecting immune responses and modulating cytokine production and inflammasome activation. However, its effects are complex, exhibiting both pro- and anti-inflammatory properties depending on dose and cell type. This review highlights the multiple mechanisms by which 4-HNE modulates the immune cells' responses.
反应性醛4-羟基-2-壬烯醛（4-HNE）是由活性氧（ROS）驱动的脂质过氧化的副产物。4-HNE与蛋白质等大分子共价结合，改变其功能。虽然4-HNE与各种ROS相关的病理过程有关，但其对免疫系统的影响仍不完全清楚。本综述探讨了4-HNE如何影响炎症和免疫细胞功能所涉及的分子机制。4-HNE通过与多种信号通路相互作用来调节炎症，包括活化B细胞核因子κB（NF-κB）、核因子红细胞2相关因子（Nrf2）、丝裂原活化蛋白激酶（MAPK）、Toll样受体（TLR）4和干扰素基因刺激因子（STING），从而影响免疫反应并调节细胞因子产生和炎性小体激活。然而，其作用是复杂的，根据剂量和细胞类型表现出促炎和抗炎特性。本综述强调了4-HNE调节免疫细胞反应的多种机制。
