Interleukin-22 ameliorated acetaminophen-induced kidney injury by inhibiting mitochondrial dysfunction and inflammatory responses

Acetaminophen (APAP) overdose can lead to acute, severe kidney injury, which has recently attracted considerable attention among researchers and clinicians. Unfortunately, there are no well-established treatments for APAP-induced renal injury, and the molecular mechanism of APAP-induced kidney injury is still unclear. Herein, we explored the protective effects of interleukin (IL)-22 on APAP-induced renal injury and the underlying molecular basis. We found that IL-22 could significantly alleviate the accumulation of reactive oxygen species (ROS) and ameliorate mitochondrial dysfunction, reducing APAP-induced renal tubular epithelial cell (TEC) death in vitro and in vivo. Furthermore, IL-22 could downregulate the APAP-induced NLRP3 inflammasome activation and mature IL-1 beta release in kidney injury. Additionally, the APAP-mediated upregulation of the serum levels of IL-18, TNF-alpha, IL-6, and IL-1 beta was obviously decreased, suggesting IL-22 has inhibitory effects on inflammatory responses. Conclusively, our study demonstrated that IL-22 exerted ameliorative effects on APAP-induced kidney injury by alleviating mitochondrial dysfunction and NLRP3 inflammasome activation, suggesting that IL-22 represents a potential therapeutic approach to treat APAP-induced kidney injury.

对乙酰氨基酚（APAP）过量可导致急性、严重的肾损伤，这最近在研究人员和临床医生中引起了相当大的关注。不幸的是，对于APAP诱导的肾损伤没有完善的治疗方法，而且APAP诱导肾损伤的分子机制仍不清楚。在此，我们探讨了白细胞介素（IL）-22对APAP诱导的肾损伤的保护作用及其潜在的分子基础。我们发现IL - 22可显著减轻活性氧（ROS）的积累并改善线粒体功能障碍，在体外和体内减少APAP诱导的肾小管上皮细胞（TEC）死亡。此外，IL - 22可下调APAP诱导的NLRP3炎症小体激活以及肾损伤中成熟的IL - 1β释放。另外，APAP介导的血清IL - 18、肿瘤坏死因子 - α、IL - 6和IL - 1β水平的上调明显降低，表明IL - 22对炎症反应具有抑制作用。总之，我们的研究表明，IL - 22通过减轻线粒体功能障碍和NLRP3炎症小体激活对APAP诱导的肾损伤发挥改善作用，这表明IL - 22是治疗APAP诱导的肾损伤的一种潜在治疗方法。