Spermidine inhibits LPS-induced pro-inflammatory activation of macrophages by acting on Nrf2 signaling but not autophagy

• Published in: Journal of functional foods 2022-07, Vol.94, p.105115, Article 105115
• Main Authors: Guo, Fang-Fang, Meng, Fan-Ge, Zhang, Xiu-Ning, Zeng, Tao
• Format: Article
• Language: English
• Subjects: Autophagy; Macrophage; Nrf-2; Spermidine
• ISSN: 1756-4646; 2214-9414
• DOI: 10.1016/j.jff.2022.105115

[Display omitted] •Spermidine suppresses LPS-induced pro-inflammatory activation of RAW264.7 cells.•Nrf-2 inducers, but not autophagy agonists, inhibit LPS-induced activation of RAW264.7 cells.•Nrf-2 knockout blunts the modulation of spermidine on LPS-driven inflammatory activation of macrophages.•Spermidine protects against LPS-induced NF-κB and NLRP3 activation in mice livers. This study was designed to investigate the roles of spermidine on lipopolysaccharide (LPS)-induced macrophage activation and underlying mechanisms. Spermidine was found to induce a moderate activation of autophagy but robust activation of nuclear factor erythroid 2-related factor 2 (Nrf-2) in a murine macrophage cell line RAW264.7 cells. Spermidine blunted LPS-driven proinflammatory activation of RAW264.7 cells evidenced by the reduced release of NO, TNF-α, and reactive oxygen species (ROS). The effects of spermidine were not affected by the autophagy inhibitor, while the autophagy inducers could not block the activation of macrophages induced by LPS. Interestingly, Nrf-2 inducers significantly suppressed the secretion of NO and TNF-α in RAW264.7 cells exposed to LPS, while the roles of spermidine were significantly blunted by the knockout of Nrf-2. Furthermore, spermidine suppressed the activation of NF-κB and the NLRP3 inflammasome in mouse liver. Collectively, spermidine could suppress LPS-induced macrophages activation possibly by activating Nrf-2 in macrophages.