Induction of MTHFD2 in Macrophages Inhibits Reactive Oxygen Species-mediated NF- κB Activation and Protects against Inflammatory Responses

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.PMID:38407485 | DOI:10.4049/jimmunol.2300209
Source: Journal of Immunology - Category: Allergy & Immunology Authors: Source Type: research