1. Academic Validation
  2. Interleukin-22 ameliorated acetaminophen-induced kidney injury by inhibiting mitochondrial dysfunction and inflammatory responses

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

  • Appl Microbiol Biotechnol. 2020 Jul;104(13):5889-5898. doi: 10.1007/s00253-020-10638-4.
Yilan Shen  # 1 Xin Jin  # 2 Wei Chen  # 2 3 Congrong Gao  # 4 Qi Bian 1 Jiajun Fan 2 Jingyun Luan 2 Zhonglian Cao 2 Zhiyong Guo 1 Yuting Gu 2 Hongrui Liu 2 Dianwen Ju 5 Xiaobin Mei 6
Affiliations

Affiliations

  • 1 Department of Nephrology, Changhai Hospital, Second Military Medical University, Shanghai, 200433, China.
  • 2 Department of Biological Medicines & Shanghai Engineering Research Center of Immunotherapeutics, Fudan University School of Pharmacy, Shanghai, 201203, China.
  • 3 Department of Ophthalmology, Stanford University School of Medicine, Palo Alto, CA, 94304, USA.
  • 4 Department of Geratology, Changhai Hospital, Second Military Medical University, Shanghai, 200433, China.
  • 5 Department of Biological Medicines & Shanghai Engineering Research Center of Immunotherapeutics, Fudan University School of Pharmacy, Shanghai, 201203, China. [email protected].
  • 6 Department of Nephrology, Changhai Hospital, Second Military Medical University, Shanghai, 200433, China. [email protected].
  • # Contributed equally.
Abstract

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-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: • IL-22 could ameliorate APAP that triggered oxidative stress and mitochondrial dysfunction. • IL-22 could reduce APAP that caused inflammatory responses. Graphical abstract.

Keywords

Acute kidney injury; Inflammatory responses; Interleukin-22; Mitochondria dysfunction.

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