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 κB (NF-κB) signaling. These changes were reversed following irisin treatment. Our study demonstrated that irisin countered LPS-mediated liver injury via inhibiting apoptosis, NLRP3 inflammasome activation and NF-κB 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.

中文翻译：

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鸢尾素通过抑制 NLRP3 炎症小体和 NF-κB 信号传导减轻 LPS 诱导的肝损伤和炎症

脂多糖 (LPS) 在败血症中引起严重的炎症和细胞死亡，肝脏是主要受影响的器官。迄今为止，对于 LPS 诱导的肝损伤，无论是作用机制还是靶向治疗都不是现成的。本研究使用动物和细胞模型研究了鸢尾素（一种内源性激素肽）对 LPS 诱导的肝损伤的影响，以及特别关注细胞焦亡的机制。众所周知，鸢尾素可调节葡萄糖代谢、炎症和免疫反应，而我们早期的工作表明鸢尾素具有抗炎和抗凋亡特性。还检测到炎症因子和 AST/ALT。分别使用 PI 染色、TUNEL 染色、DCFH-DA 荧光和蛋白质印迹评估细胞焦亡、细胞凋亡和活性氧 (ROS)。我们的结果表明，鸢尾素减轻了 LPS 诱导的肝损伤和炎性细胞因子的释放。在 LPS 攻击的 Raw264.7 细胞中发现 NLRP3 炎症小体的活性增加，同时炎症和细胞凋亡水平升高，其影响是由 ROS 和核因子 κB (NF-κB) 信号传导介导的。这些变化在鸢尾素治疗后逆转。我们的研究表明，鸢尾素通过抑制细胞凋亡、NLRP3 炎症小体激活和 NF-κB 信号传导来对抗 LPS 介导的肝损伤。这些发现揭示了鸢尾素作为一种有前途的新型抗细胞焦亡/细胞凋亡剂的作用，以协调败血性肝损伤的发生和进展。在 LPS 攻击的 Raw264.7 细胞中发现 NLRP3 炎症小体的活性增加，同时炎症和细胞凋亡水平升高，其影响是由 ROS 和核因子 κB (NF-κB) 信号传导介导的。这些变化在鸢尾素治疗后逆转。我们的研究表明，鸢尾素通过抑制细胞凋亡、NLRP3 炎症小体激活和 NF-κB 信号传导来对抗 LPS 介导的肝损伤。这些发现揭示了鸢尾素作为一种有前途的新型抗细胞焦亡/细胞凋亡剂的作用，以协调败血性肝损伤的发生和进展。在 LPS 攻击的 Raw264.7 细胞中发现 NLRP3 炎症小体的活性增加，同时炎症和细胞凋亡水平升高，其影响是由 ROS 和核因子 κB (NF-κB) 信号传导介导的。这些变化在鸢尾素治疗后逆转。我们的研究表明，鸢尾素通过抑制细胞凋亡、NLRP3 炎症小体激活和 NF-κB 信号传导来对抗 LPS 介导的肝损伤。这些发现揭示了鸢尾素作为一种有前途的新型抗细胞焦亡/细胞凋亡剂的作用，以协调败血性肝损伤的发生和进展。我们的研究表明，鸢尾素通过抑制细胞凋亡、NLRP3 炎症小体激活和 NF-κB 信号传导来对抗 LPS 介导的肝损伤。这些发现揭示了鸢尾素作为一种有前途的新型抗细胞焦亡/细胞凋亡剂的作用，以协调败血性肝损伤的发生和进展。我们的研究表明，鸢尾素通过抑制细胞凋亡、NLRP3 炎症小体激活和 NF-κB 信号传导来对抗 LPS 介导的肝损伤。这些发现揭示了鸢尾素作为一种有前途的新型抗细胞焦亡/细胞凋亡剂的作用，以协调败血性肝损伤的发生和进展。