Irisin alleviates LPS-induced liver injury and inflammation through inhibition of NLRP3 inflammasome and NF-κB signaling

作者：Li, Qian; Tan, Ying; Chen, Sainan; Xiao, Xiaochan; Zhang, Mingming; Wu, Qi; Dong, Maolong^*

来源：Journal of Receptor and Signal Transduction Research, 2021, 41(3): 294-303.

DOI：10.1080/10799893.2020.1808675

• Irisin
• inflammation
• LPS
• macrophage
• pyroptosis
• septic liver injury

Lipopolysaccharide (LPS) provokes severe inflammation and cell death in sepsis, with liver being the major affected organ. Up-to-date, neither the mechanism of action nor target treatment is readily available for LPS-induced liver injury. This study examined the effect of irisin, an endogenous hormonal peptide, on LPS-induced liver injury using animal and cell models, and the mechanism involved with a special focus on pyroptosis. Irisin is known to regulate glucose metabolism, inflammation, and immune response, while our earlier work denoted the anti-inflammatory and anti-apoptotic properties for irisin. Inflammatory factors and AST/ALT were also detected. Pyroptosis, apoptosis, and reactive oxygen species (ROS) were evaluated using PI staining, TUNEL staining, DCFH-DA fluorescence, and western blot, respectively. Our results indicated that irisin attenuated LPS-induced liver injury and release of inflammatory cytokines. Increased activity of NLRP3 inflammasome was discovered in LPS-challenged Raw264.7 cells, along with elevated levels of inflammation and apoptosis, the effects of which were mediated by activation of ROS and nuclear factor kappa B (NF-kappa B) signaling. These changes were reversed following irisin treatment. Our study demonstrated that irisin countered LPS-mediated liver injuryviainhibiting apoptosis, NLRP3 inflammasome activation and NF-kappa B signaling. These findings revealed the role of irisin as a promising new anti-pyroptosis/apoptosis agent to reconcile the onset and progression of septic liver injury.

• 单位
  南方医科大学