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

• Published in: Applied microbiology and biotechnology Vol. 104; no. 13; pp. 5889 - 5898
• Main Authors: Shen, Yilan, Jin, Xin, Chen, Wei, Gao, Congrong, Bian, Qi, Fan, Jiajun, Luan, Jingyun, Cao, Zhonglian, Guo, Zhiyong, Gu, Yuting, Liu, Hongrui, Ju, Dianwen, Mei, Xiaobin
• Format: Journal Article
• Language: English
• Published: Berlin/Heidelberg Springer Berlin Heidelberg 01-07-2020; Springer; Springer Nature B.V
• Subjects: Acetaminophen; Acetaminophen - toxicity; Activation; Acute Kidney Injury - chemically induced; Acute Kidney Injury - drug therapy; Acute Kidney Injury - pathology; Analgesics; Animals; Applied Microbial and Cell Physiology; Biomedical and Life Sciences; Biotechnology; Cell death; Cell Line; Cell Survival - drug effects; Cytokines; Cytokines - metabolism; Epithelial cells; Humans; IL-1β; Inflammasomes; Inflammasomes - drug effects; Inflammasomes - metabolism; Inflammation; Injuries; Interleukin 18; Interleukin 22; Interleukin 6; Interleukins; Interleukins - therapeutic use; Kidney - drug effects; Kidney - injuries; Kidney - physiopathology; Kidneys; Life Sciences; Male; Mice; Mice, Inbred C57BL; Microbial Genetics and Genomics; Microbiology; Mitochondria; Mitochondria - drug effects; Mitochondria - metabolism; Overdose; Oxidative stress; Oxidative Stress - drug effects; Reactive oxygen species; Reactive Oxygen Species - metabolism; Renal function; Serum levels; Tumor necrosis factor-α; China; Inflammatory responses; Interleukin-22; Mitochondria dysfunction; Acute kidney injury
• ISSN: 0175-7598; 1432-0614
• DOI: 10.1007/s00253-020-10638-4

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
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Furthermore, IL-22 could downregulate the APAP-induced NLRP3 inflammasome activation and mature IL-1β release in kidney injury. Additionally, the APAP-mediated upregulation of the serum levels of IL-18, TNF-α, IL-6, and IL-1β 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.
Key Points
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IL-22 could ameliorate APAP that triggered oxidative stress and mitochondrial dysfunction.
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IL-22 could reduce APAP that caused inflammatory responses.
Graphical abstract