活性氧
促炎细胞因子
化学
TLR4型
细胞生物学
NF-κB
巨噬细胞
细胞因子
免疫系统
炎症
免疫学
生物
生物化学
体外
作者
You-qiang Cui,Zihan Li,Lina Ni,Shimeng Yu,Xiaonan Shan,Penghui Hu,Zemin Ji,Jing Wei,Yanzhao Zhou,Baochen Wang,Huijuan Dong,Jinxue Zhou,Keliang Xie,Qiujing Yu
出处
期刊:Journal of Immunology
[The American Association of Immunologists]
日期:2024-02-26
卷期号:212 (8): 1345-1356
标识
DOI:10.4049/jimmunol.2300209
摘要
The one-carbon metabolism enzyme methylenetetrahydrofolate dehydrogenase 2 (MTHFD2) is critical for cancer cell proliferation and immune cell phenotypes, but whether it can contribute to macrophage inflammatory responses remains unclear. In this study, we show that MTHFD2 was upregulated by LPS in murine macrophages upon activation of the TLR4-MyD88-IKKα/β-NF-κB signaling pathway. MTHFD2 significantly attenuated LPS-induced macrophage proinflammatory cytokine production through its enzymatic activity. Notably, ablation of myeloid MTHFD2 rendered mice more sensitive to septic shock and CCl4-induced acute hepatitis. Mechanistically, MTHFD2 restrained IKKα/β-NF-κB activation and macrophage inflammatory phenotype by scavenging reactive oxygen species through the generation of NADPH. Our study reveals MTHFD2 as a "self-control" mechanism in macrophage-mediated inflammatory responses.
科研通智能强力驱动
Strongly Powered by AbleSci AI